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Liver tissue of doxorubicin plus CAPE given group. There is no mononuclear cell infiltration (H-E, 20x).
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The aim of this study was to compare the possible protective effects of N-acetylcysteine (NAC), caffeic acid (CAPE) and vitamin E (Vit-E) on doxorubicin-induced hepatotoxicity. Thirty-two male Wistar albino rats, weighing between 250 and 350 g were supplied and randomly divided into five groups. Animals in study groups were pretreated with a single...
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Context 1
... was no difference between doxorubicin and N-acetyl cystein given groups (P 0.05) (Figure 2). There was no mononuclear cell infiltration, sinusoidal or central vein dilatation and minimal hepatocyte degeneration in doxorubicin plus CAPE given group, when compared with only doxorubicin given group (P 0.05) (Figure 3). There was more remarkable recovery in vitamin E given group, when compared with doxorubicin plus CAPE given group (Figure 4). ...
Context 2
... by Dox. Histopathologic examination revealed that Dox- induced deleterious changes in heart and liver tissues were offset by LMWH treatment. Restoration of cellular structure implies the cytoprotective role of LMWH in doxorubicin-induced cardiac and hepatic toxicity. 15 Vitamin-E and catechin signifi- cantly reduce doxorubicin-induced hepatotoxicity in rats. 16 It has been reported that Dox related changes observed in both heart and liver tissues were diminished by CAR administration at cellular level. This result suggests that CAR is potentially a hepato- protectant agent in Dox-induced hepatotoxicity. 12 N-acetylcysteine (NAC) is a chemical compound produced by the body, which enhances the production of glutathione, a powerful antioxidant. NAC is a thiol, in which hydrogen atoms can act to reduce free radicals. Glutathione inhibits hepatic microso- mal lipid peroxidation initiated by the redox-cycling of doxorubicin. Inhibition of doxorubicin-dependent lipid peroxidation appears to be enzyme-mediated and it probably requires tocopherol. 17 Caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, is known to have antimitogenic, anticarcinogenic, antiinflammatory and immunomodulatory properties. Molecular basis of these diverse properties is not clear. 18 It has been suggested that CAPE has protective effect against cisplatin-induced oxidative changes in liver tissue. It empowers the antioxidant defence system via reducing reactive oxygen species (ROS) and increasing antioxidant enzyme activity. 19 The main goal of the current study was to compare the protective effects of NAC, CAPE and vitamin E on DOX induced hepatotoxicity. Yet, there is no such study in the literature in which the effects of both CAPE and doxorubicin on liver tissue were evaluated. Thirty male 12–15-week old Wistar Albino rats weighting between 250 and 300 g were obtained with specific-pathogen-free (SPF) status from Animal Laboratory of Suleyman Demirel University School of Medicine. All animals were kept under standard laboratory conditions. 20 Filtrated municipal tap water (Isparta, Turkey) and standard laboratory rat feed (Abalıo glu Yem Sanayii, Denizli, Turkey) were pro- vided ad libitum . Feed and water consumption were followed daily after the acclimatisation period. Rats were randomly divided into five groups as follows: Controls ( n ϭ 6), doxorubicin treated group ( n ϭ 6), NAC given group ( n ϭ 6), vitamin-E given group ( n ϭ 6) and CAPE administered group ( n ϭ 6). All rats in experimental groups were initially treated with a single dose of 20 mg/kg doxorubicin (Dox) administered intraperitoneally (i.p.). Control group (Group I) was only given saline in the same way. Experimental groups (Group II) were not given any antioxidant agent after injection. Group III was administered CAPE and Group IV was given intraperitoneal Vit-E for eight days. Group V was orally given NAC for eight days. The study was finished after 10 days. Tissue samples were collected and histopathological examination was performed (Table 1). All animals were decapitated under ether anesthesia. Liver tissue samples were collected for histological examination. Tissues were fixated in 10% neutral formaline solution. After performing routine tissue processing procedures, samples were embedded in paraffin blocks. For microscopic evaluation, 15 sections were cut from each block by using systematical randomized sampling method. All sections were stained with hematoxyline-eosine dye. Stained sections were examined under Olympus-BX 50 light microscope. The main portal area diameters were calculated as the mean diameter [(t r ϩ v r ) / 2] from the vertical (v r ) and transverse (t r ) diameters measured by an ocular micrometer for 100 portal areas with 10-fold magnification. Mean sinusoidal width was an aver- age of 1000 measurements. 21 The method of Tsuhamoto and Towner 22 was modified to evaluate the hepatocyte degeneration, as follows: 1 ϩ ϭ 0–25% of hepatocytes with degeneration (lit- tle); 2 ϩ ϭ 25–50% (median); 3 ϩ ϭ 50–75% (high); and 4 ϩ Ͼ 75% (very high). All data were presented as mean value Ϯ standard deviation (SD). Two-tailed t -test method was used to compare the mean values. Statistical analysis was performed by using Statistica 6.0 software. P -values under 0.05 were considered as statistically significant. There was a significant difference between the doxorubicin-treated group and controls by means of mononuclear cell infiltration, sinusoidal, central vein and portal triad diameters ( P Ͻ 0.05) (Figure 1). Hepatocyte degeneration was more prominent in only doxorubicin given group ( P Ͻ 0.001). There was no difference between doxorubicin and N-acetyl cystein given groups ( P Ͼ 0.05) (Figure 2). There was no mononuclear cell infiltration, sinusoidal or central vein dilatation and minimal hepatocyte degeneration in doxorubicin plus CAPE given group, when compared with only doxorubicin given group ( P Ͻ 0.05) (Figure 3). There was more remarkable recovery in vitamin E given group, when compared with doxorubicin plus CAPE given group (Figure 4). Hepatocyte degeneration was more significant in only doxorubicin and doxorubicin plus NAC given groups, when compared with the controls and other groups ( P Ͻ 0.01). Mean sinusoidal, central vein and portal triad diameters were shown in Figure 5–7. Doxorubicin (adriamycin) is a well known antineoplastic and antibiotic agent, which is widely used in cancer treatment. There are so many studies which have been conducted to reveal the exact role of this agent in hepatotoxicity to date. It has been reported that doxorubicin caused severe damage in some organs like liver, heart and kidneys. Pedrycz et al., have reported that there was a persistent and irre- versible damage in hepatic tissue after adriamycin treatment. 23 They have also reported that focal damage in hepatocytes, significant steatosis and vascular damage were present. 11 In our study, we have observed some histopathological changes such as dilatation in sinusoids, central veins and portal triads, mononuclear cell infiltration and hepatocyte degeneration. Free radical formation was suggested to be involved in doxorubicin-induced hepatotoxicity mechanism. Two different mechanisms have been identified. In the first mechanism, semiquinone type free radical molecules are produced via NADPH-dependent reductase enzyme pathway. Quinone and semiquinone derivatives originated from doxorubicin give rise to superoxide radicals by reacting with oxygen. In the second mechanism, doxorubicin interacts with the iron ions such as ferritin and leads to free radical production by a non-enzymatic reaction. This kind of interaction may result in a complex of iron and doxorubicin, which can reduce oxygen to other radical oxygen species. 3 It has been reported that doxorubicin may lead to the production of superoxide anion radicals, H 2 O 2 and hydroxyl radicals in rats. 24 In a study by Ganey et al. , it has been reported that in oxygen-rich areas of the liver, doxorubicin-mediated redox cycle was higher and also a decrement in NADPH fluores- cence was determined in periportal areas of the liver, when compared with the pericentral areas. 25 In the current study, no significant change was present in histopathological examination of doxorubicin plus NAC group, when compared with only doxorubicin given group. In previous studies, it was reported that NAC has no protective effect in doxorubicin induced hepatotoxicity. Furthermore, NAC may also lead to some unexpected results such as toxicity and degeneration in liver tissue. Doroshow et al. have reported that there was an injury pattern similiar to the doxorubicin hepatotoxicity, which also includes lipid droplet accumulation and cytoplasmic atte- nuation in liver tissues of animals pretreated with NAC. They have also indicated that NAC pretreatment does not have any effect on pharmacokinetic profile or metabolism of doxorubicin in heart or liver. 24 Caffeic acid phenethyl ester has anti-inflammatory, immunomodulatory and antioxidant effects. 26 CAPE exhibits its antioxidant effect in various oxidant conditions that cause tissue injury. 27–29 In our study, mononuclear cell infiltration, decrease in hepatocyte degeneration or dilatation were not observed in doxorubicin plus CAPE given group. This evidence is in parallel to the data from previous studies. It is known that doxorubicin shows its toxic effects mainly via lipid peroxidation way. Vitamin E pre- vents lipid peroxidation via its robust free radical scanvengering effect. Yet, it seems that inhibition of doxorubicin induced lipid peroxidation involves an enzyme-based mechanism and can be avoided by vitamin E. 17 We found that there was no significant difference between the controls and doxorubicin plus vitamin E given group and this evidence is in corre- lation with the previous data. This suggests vitamin E may inhibit general toxic and hepatotoxic effects of doxorubicin. Also, we have concluded that the protective effect of vitamin E treatment was more effec- tive than the others and doxorubicin induced hepatotoxicity could be avoided by using vitamin E or CAPE, but not NAC. This negative effect of doxorubicin is reversible. By conducting further studies, underlying mechanisms in doxorubicin-mediated toxicity and efficacy of antioxidant treatment would be explained ...
Citations
... FGF1 was reported to have antioxidative activities against diabetes associated NAFLD [21] and DOX-induced hepatoxicity [27], and hepatic oxidative stress was thought to paly causal roles in the development of DOX-induced hepatoxicity, since supplement of an antioxidant compound N-acetyl cysteine significantly attenuated DOX-induced liver damage [29][30][31]. Thus, we assumed that FGF1 deletion might exacerbate hepatic oxidative stress, contributing to the aggravated development of DOX-induced liver damage in FGF1-KO mice. ...
Doxorubicin (DOX) is a broad-spectrum antineoplastic agent that widely used in clinic. However, its application is largely limited by its toxicity in multiple organs. Fibroblast growth factor 1 (FGF1) showed protective potential in various liver diseases, but the role of endogenous FGF1 in DOX-induced liver damage is currently unknown. Both wild-type (WT) and FGF1 knockout (FGF1-KO) mice were treated with DOX. DOX induced loss of body weight and liver weight and elevation of ALT and AST in WT mice, which were aggravated by FGF1 deletion. FGF1 deletion exacerbated hepatic oxidative stress mirrored by further elevated 3-nitrosative modification of multiple proteins and malondialdehyde content. These were accompanied by blunted compensatively antioxidative responses indicated by impaired upregulation of nuclear factor erythroid 2-related factor 2 and its downstream antioxidant gene expression. The aggravated oxidative stress was coincided with exacerbated cell apoptosis in DOX-treated FGF1-KO mice reflected by further increased TUNEL positive cell staining and BCL-2-associated X expression and caspase 3 cleavage. These detrimental changes in DOX-treated FGF1-KO mice were associated with worsened intestinal fibrosis and increased upregulation fibrotic marker connective tissue growth factor and α-smooth muscle actin expression. However, DOX-induced hepatic inflammatory responses were not further affected by FGF1 deletion. These results demonstrate that endogenous FGF1 deficiency aggravates DOX-induced liver damage and FGF1 is a potential therapeutic target for treatment of DOX-associated hepatoxicity.
... 10,11 However, administration of the glutathione donor N-acetyl cysteine (NAC) failed to improve sinusoidal dilation and mononuclear infiltration following acute doxorubicin challenge. 12 Thus, mitigation of doxorubicin-induced oxidative stress is insufficient to protect the liver from damage especially following chronic drug exposure. ...
Off target damage to vital organ systems is an unfortunate side effect of cancer chemotherapy and remains a major limitation to the use of these essential drugs in the clinic. Despite decades of research, the mechanisms conferring susceptibility to chemotherapy driven cardiotoxicity and hepatotoxicity remain unclear. In the livers of patients with a history of chemotherapy, we observed a twofold increase in expression of G protein regulator RGS7 and a corresponding decrease in fellow R7 family member RGS11. Knockdown of RGS7 via introduction of RGS7 shRNA via tail vein injection decreased doxorubicin‐induced hepatic collagen and lipid deposition, glycogen accumulation, and elevations in ALT, AST, and triglycerides by approximately 50%. Surprisingly, a similar result could be achieved via introduction of RGS7 shRNA directly to the myocardium without impacting RGS7 levels in the liver directly. Indeed, doxorubicin‐treated cardiomyocytes secrete the endocrine factors transforming growth factor β1 (TGFβ1) and TGFβ superfamily binding protein follistatin‐related protein 1 (FSTL1). Importantly, RGS7 overexpression in the heart was sufficient to recapitulate the impacts of doxorubicin on the liver and inhibition of TGFβ1 signaling with the receptor blocker GW788388 ameliorated the effect of cardiac RGS7 overexpression on hepatic fibrosis, steatosis, oxidative stress, and cell death as well as the resultant elevation in liver enzymes. Together these data demonstrate that RGS7 controls both the release of TGFβ1 from the heart and the profibrotic and pro‐oxidant actions of TGFβ1 in the liver and emphasize the functional significance of endocrine cardiokine signaling in the pathogenesis of chemotherapy drive multiorgan damage.
... 67 However, Gokcimen et al. and Gross concluded that vitamin E has a protective effect on doxorubicin hepatotoxicity. 68,69 Levocarnitine has also shown a protective effect against hepatotoxicity induced by doxorubicin. [70][71][72] It is evident from this study that there was a significant increase in the serum Bil levels in the IG compared to the CG group (Table 6); however, no differences were found in the two groups for the liver enzymes (AST, ALT and ALK). ...
Background:
Doxorubicin induces acute and chronic cardiotoxicity. This study is aimed to evaluate the efficacy and safety of vitamin E and levocarnitine (EL) as cardioprotective agents against acute doxorubicin cardiotoxicity in female adult breast cancer patients.
Methods:
A prospective, randomized controlled study was conducted in patients treated with doxorubicin and cyclophosphamide (AC). Patients were randomly assigned to EL plus AC or AC alone for the duration of 4 cycles. Cardiac enzymes (B-type natriuretic peptide, creatine kinase, troponin I (Trop)) and cardiac events were monitored during treatment to evaluate the cardioprotective efficacy of EL.
Results:
Seventy-four patients were recruited and received four cycles of chemotherapy. The intervention group (n = 35) showed a significant reduction in both the B-type natriuretic peptide and creatine kinase cardiac enzymes compared to the control group (n = 39). The median (IQR) change for BNP was 0.80 (0.00-4.00) for IG versus 1.80 (0.40-3.60) for CG groups (p < 0.001); creatine kinase was -0.08 (-0.25-0.05) for IG versus 0.20 (0.05-0.50) for CG (p < 0.001). The addition of EL decreased the cardiac events by 24.2% (p = 0.02). All adverse events were tolerable and manageable.
Conclusion:
This study supports the addition of EL as prophylaxis against acute doxorubicin cardiotoxicity and it was also very well tolerated by a majority of the patients. The co-administration of EL at higher doxorubicin (240 mg/m2) dose should be further investigated.
... Also, in a study by Pakravan et al. (2017) was found that administration of Melatonin in a duration of 6 weeks in patients with NAFLD can reduce AST significantly compared to the placebo group but ALT level was not changed significantly. Gokcimen et al. (2007) in an animal intervention study after histopathological examination found that N-acetylcysteine had no protective effect on the liver in doxorubicin induced hepatotoxicity. In contrast, Baniasadi et al. (2010) showed that receiving 600mg NAC orally twice a day can protect liver against anti TB drug induced damage. ...
... Herein, we found that VE treatment together with KBrO 3 alleviated the elevated activities of the markers of hepatocellular injury AST, ALT and ALP comparing with KBrO 3 treated rats. Various experimental research on the animal species showed that VE treatment ameliorated liver damage induced by carbon tetrachloride 46 , doxorubicin, anthracycline antibiotic 47 , and pesticides such as malathion 48 . Similar observation was reported in mice where VE ameliorated organophosphorus insecticide (diazinon) induced oxidative stress in mice liver 49 . ...
... Spotty necrosis, venous congestion, sinusoidal congestion, inflammation, and Kupffer cell hyperplasia serve as indicators of hepatic tissue damage [58,59]. In the present and previous studies, similar histopathological findings have also been identified in both EAC mice [60] and doxorubicin-treated animals [61]. However, in this study, animals treated with DOX alone did not show any improvement in spotty necrosis but showed reduced venous congestion, sinusoidal congestion, and inflammation. ...
Background and objective:
Doxorubicin is a widely used chemotherapeutic agent that causes oxidative stress leading to cardiotoxicity, hepatotoxicity, and nephrotoxicity. In contrast, Theobroma cacao L. has been recorded as an anticancer agent and found to be protective against multiple chemical-induced organ injuries, including heart, liver, and kidney injuries. The present study investigated the possible role of extracts from T. cacao beans for organ-protective effects in doxorubicin-induced toxicity in mice bearing Ehrlich ascites carcinoma (EAC).
Methodology:
After survival analysis in rodents, cocoa bean extract (COE) was investigated for its efficacy against EAC-induced carcinoma and its organ-protective effect against doxorubicin-treated mice with EAC-induced carcinoma.
Results:
Significant reductions in EAC and doxorubicin-induced alterations were observed in mice administered the COE, either alone or in combination with doxorubicin. Furthermore, COE treatment significantly increased the mouse survival time, life span percentage, and antioxidant defense system. It also significantly improved cardiac, hepatic, and renal function biomarkers and markers for oxidative stress, and it also reduced doxorubicin-induced histopathological changes.
Conclusion:
COE acted against doxorubicin-induced organ toxicity; potent antioxidant and anticancer activities were also reflected by the COE itself. The COE may therefore serve as an adjuvant nutraceutical in cancer chemotherapy.
... According to [1], residual amounts of organochlorine organophosphate pesticides have been detected in soil, water reservoirs, vegetables, grains and other food products. Activation of cholinergic receptors by Organophosphate pesticides has been reported in experimental animals [2,3]. ...
Aim: This study was aimed at evaluating the effect of lycopene on some selected electrolytes in Sprague Dawley rats exposed to Dimethoate. Experimental Design: A completely randomized experimental design using standard methods for analysis. Location and Duration of Study: This study was carried out in the Department of Biology, Ignatius Ajuru University of Education Rumuolumeni, Port Harcourt, Rivers State, Nigeria. GPS 4o48ʹ14ʹʹ N 6o59ʹ12ʹʹ E. The study lasted for 28days. Methodology: Thirty male rats were randomly selected into five (5) groups A-E (n=6/group). Groups B, C and D recieved 10,20 and 30 mg/kg/bw/day of dimethoate respectively co-administered 10mg/kg/bw of lycopene daily. Group E were administered 30mg/kg/bw/day of dimethoate without lycopene. All animals were allowed access to cool clean water and standard rat pellet ad libitum. Twenty-four hours to the termination of the experiment, feed was withdrawn from the animals. Blood samples for electrolytes analysis were collected through ocular puncture between the hours of 7:00am and 9:00am into plain sample tubes according to the approved protocol of blood collection techniques, while statistical analysis was carried out using one-way Analysis of Variance (ANOVA) and expressed as their respective units using SPSS 20 software. Results: Result showed a significant (P=0.05) increase in the concentrations of sodium, calcium, potassium and bicarbonate with increase in the concurrent administration of lycopene. The highest concentration of all electrolytes was observed at the concentration of 30mg/kg/bw/day with coadministration of lycopene. Administration of lycopene at the concentration of 10mg/kg/bw appeared not to have any significant effect on production of electrolytes since all the electrolytes assessed increased with increased concentration of the pesticides. However, further work is required to make any conclusive statement with lycopene effect on electrolyte.
... half-life of the drug (20-48 h), slow rate of drug absorption when administered intraperitoneally, and based on the experimental protocols followed in previous studies (Oz and Ilhan, 2006;Gokcimen et al., 2007;Turner et al., 2011;Package insert;Doxutec, United Biotech, India). The existence of kidney injury in ADM-induced rats was confirmed by estimating urine total protein concentration one week after induction of nephrotoxicity by using ADM. ...
Absteact
Ethnopharmacological relevance
Ambrette (Abelmoschus moschatus Medik., Family: Malvaceae) is a common Ayurvedic herbal medicine used in the treatment of kidney-related diseases, in the forms of tea, medicated oil, medicated wine, etc., however, its nephroprotective mechanisms remain unexploited.
Aim of the study
To investigate the mechanisms by which the hexane (A-HE), ethyl acetate (A-EE), butanol (A-BE), and aqueous (A-WE) leaf extracts of Ambrette protect against the adriamycin-mediated acute kidney injury in Wistar rats.
Materials and methods
A-HE, A-EE, A-BE, A-WE, and fosinopril sodium were administered at therapeutically effective doses (55, 75, 60, 140, 0.09 mg/kg) to adriamycin-induced (5 mg/kg, ip) Wistar rats for 28 consecutive days.
Results
Oral administration of the selected extracts of A. moschatus resulted in amelioration of kidney injury as observed by the significant changes of biomarkers of kidney function in serum and in urine, biochemical parameters of oxidative stress, and inflammation in kidney homogenates (p < 0.05). Furthermore, the administration of plant extracts caused a significant reduction in total kidney injury scores in H and E stained kidney sections (p < 0.05). The immunohistochemical expression of the inflammatory marker, COX-2, and the pro-apoptotic marker, Bax, were attenuated and the expression of the anti-apoptotic marker, BCL-2, was increased. A-HE exerted superior nephroprotective effects over the other three extracts and the drug reference standard.
Conclusions
The findings revealed that Ambrette exerts promising protective effects against adriamycin-mediated acute kidney injury through antioxidant, anti-inflammatory, and anti-apoptosis pathways. A-HE might serve as a potential candidate for the development of therapeutic drug leads that will be beneficial in the treatment of acute kidney injury.
... The DOX dosage and route of application were determined considering the previous studies investigating DOX-induced liver injury in rats. [17][18][19] In the DOX + MSC group, BM-MSCs (2 × 10 6 cells in 1 ml MEM/rat) were administered intravenously via tail vein at the 96th hour of DOX (20 mg/kg) administration. [17] The optimal number of MSCs to be administered was determined in line with the similar previous studies in the literature. ...
... [17][18][19] In the DOX + MSC group, BM-MSCs (2 × 10 6 cells in 1 ml MEM/rat) were administered intravenously via tail vein at the 96th hour of DOX (20 mg/kg) administration. [17] The optimal number of MSCs to be administered was determined in line with the similar previous studies in the literature. [20,21] Following intraperitoneal administration of a mixture of 50 mg/kg ketamine (Ketasol 10%; Richter Pharma Ag) and 5 mg/kg xylazine (Xylazinbio 2%; Bioveta) 48 h after BM-MSC administration, the abdomen was opened and blood samples were taken from the heart. ...
... [36] Previous studies have reported that lipid peroxidation due to increased ROS in DOX toxicity causes structural damage in the liver parenchyma. [8,17,29] When hepatocytes are damaged following DOX administration, ALT and AST are released into the bloodstream and this increase in the serum enzyme levels is accepted as a biochemical indicator of liver injury. [36][37][38] In the current study, DOX administration was shown to be associated with liver injury characterized by cytoplasmic vacuolization and necrosis in hepatocytes. ...
Doxorubicin (DOX) is a potent chemotherapeutic agent and has toxic effects on various organs, including the liver. In the current study, we aimed to investigate the effects of bone‐marrow‐derived mesenchymal stem cell (BM‐MSC) administration on DOX‐induced hepatotoxicity in rats. 24 Wistar‐albino rats were divided into three groups: Control, DOX, and DOX+MSC. DOX (20 mg/kg) was administered to the DOX group. In the DOX + MSC group, BM‐MSCs (2 × 106) were given through the tail vein following DOX administration. DOX administration led to significant structural liver injury. Besides this, oxidative balance in the liver was impaired following DOX administration. DOX administration also led to an increase in apoptotic cell death in the liver. Structural and oxidative changes were significantly alleviated with the administration of BM‐MSCs. Furthermore, BM‐MSC administration suppressed excessive apoptotic cell death. Our findings revealed that BM‐MSC administration may alleviate DOX‐induced liver injury via improving the oxidative status and limiting apoptotic cell death in the liver tissue.
... CA prevented SNAP-derived nitrite generation and repressed the expression of inducible nitric oxide synthase (iNOS) in RAW 264.7 macrophages, abrogated carrageenan-mediated paw oedema as well as carrageenan-induced neutrophil influx and prevented the increase in IL-1β levels in mouse paw (da Cunha et al., 2004). The observed antioxidant, anti-inflammatory and anti-apoptotic effects of CA may have contributed to its ability to abrogate hepatorenal toxicities mediated by different toxicants as previously reported: methotrexate (Oktem et al., 2006), oxytetracycline (Jayanthi and Subash, 2010), alcohol (Pari and Karthikesan, 2007), abamectin (Abdel-Daim and Abdellatief, 2018), doxorubicin (Gokcimen et al., 2007), and cadmium (Ashour, 2014). In the current study, we further narrowed the gap in aflatoxin research by evaluating the abrogative tendency of CA against AFB 1 -induced hepatorenal toxicities in male Wistar rats. ...
Aflatoxicosis can induce largescale toxicities in predisposed populations. Food fortification with adequate antioxidant sources may reduce the toxic burden from aflatoxicosis. We examined the individual and combined effect of Caffeic acid (CA) on the aflatoxin B1 (AFB1)-induced hepatic and renal injury in male rats. Five experimental rat cohort (n = 6) consisting of the control (2 mL/kg corn oil), AFB1 alone (50 μg/kg), CA alone (40 mg/kg), AFB1+CA1 (50 μg/kg + 20 mg/kg) and AFB1+CA2 (50 μg/kg + 40 mg/kg) were so treated for 28 consecutive days. Upon sacrifices, diagnostic markers of hepatorenal functions, oxidative stress, inflammation, oxidative deoxyribonucleic acid -DNA-damage and apoptosis were analysed. Our results showed that CA reduced AFB1-induced toxicities in rats' liver and kidneys by significantly increasing (p < 0.05) endogenous antioxidant and the anti-inflammatory IL-10 level. Caffeic acid simultaneously reduced hepatic and renal dysfunction biomarkers in the serum, oxidative stress, and lipid peroxidation levels. Besides, CA diminished reactive oxygen and nitrogen species, inflammatory nitric oxide levels, interleukin-1 β and the activities of xanthine oxidase and myeloperoxidase. Additionally, CA reduced DNA damage and caspase-mediated apoptotic responses and preserved the cytoarchitecture of rats' liver and kidneys treated with AFB1. These data suggest that CA can be used as a food additive to mitigate AFB1-induced toxicity in the examined organs.
