The present study investigated the individual and combined impact of organophosphorus pesticide chlorpyrifos (CPF) and manganese (Mn), a naturally occurring trace metal, on hepatorenal function in adult rats. The four experimental groups namely control, CPF alone (5 mg/kg), Mn alone (10 mg/kg) and the co-exposure group consisted of eight rats which were orally gavage for 14 consecutive days. Following sacrifice, the biomarkers of hepatorenal damage, antioxidant enzyme activities, myeloperoxidase (MPO) activity as well as levels of nitric oxide, reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were analysed spectrophotometrically. Further, the concentration of tumour necrosis factor alpha (TNF-α), interleukin-1 β (IL-1β) and caspase-3 activity were assessed using ELISA. Results showed that the CPF-induced increase in biomarkers of hepatorenal toxicity were significantly (p < 0.05) alleviated in rats co-expose to CPF and Mn. Moreover, the decrease in antioxidant status as well as the elevation in RONS and LPO were significantly assuaged in rats co-treated with CPF and Mn. In addition, CPF mediated increase in TNF-α, IL-1β and caspase-3 activity were significantly diminished in the liver and kidney of rats co-exposed to CPF and Mn. Light microscopic examination evidenced that the severity of histopathological lesions induced by CPF were alleviated in rats co-exposed to CPF and Mn. In conclusion, the results highlight that co-exposure to CPF and Mn in rats assuaged CPF-induced oxidative stress, inflammation and caspase-3 activation in the liver and kidney of the rats.

The present study investigated the antioxidant and anti-inflammatory effects of dietary protocatechuic acid (PCA), a simple hydrophilic phenolic compound commonly found in many edible vegetables, on dextran sulphate sodium (DSS)-induced ulcerative colitis and its associated hepatotoxicity in rats. PCA was administered orally at 10 mg kg⁻¹ to dextran sulphate sodium exposed rats for five days. The result revealed that administration of PCA significantly (p < 0.05) prevented the incidence of diarrhea and bleeding, the decrease in the body weight gain, shortening of colon length and the increase in colon mass index in DSS-treated rats. Furthermore, PCA prevented the increase in the plasma levels of pro-inflammatory cytokines, markers of liver toxicity and markedly suppressed the DSS-mediated elevation in colonic nitric oxide concentration and myeloperoxidase activity in the treated rats. Administration of PCA significantly protected against colonic and hepatic oxidative damage by increasing the antioxidant status and concomitantly decreased hydrogen peroxide and lipid peroxidation levels in the DSS-treated rats. Moreover, histological examinations confirmed PCA chemoprotection against colon and liver damage. Immunohistochemical analysis showed that PCA significantly inhibited cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) protein expression in the colon of DSS-treated rats. In conclusion, the effective chemoprotective role of PCA in colitis and the associated hepatotoxicity is related to its intrinsic anti-inflammatory and anti-oxidative properties.

The present study investigated the effects of aflatoxin B₁ (AFB₁) and ethanol co-exposure on biomarkers of hepatic damage in mice. Four groups of adult male mice were treated for 7 consecutive days. Control mice received corn oil alone at a dose of 2 mL/kg bw. One group was treated with ethanol at a dose of 500 µL/kg bw and another group administered 9 mg/kg bw of AFB₁ dissolved in corn oil. The fourth group was co-administered with ethanol and AFB ₁. The body and liver weights of treated mice decreased significantly when compared with corresponding control. Alone, ethanol and AFB₁ treatment separately increased serum activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP). Alcohol dehydrogenase (ALD) activity was markedly elevated in ethanol-treated mice but was unaffected by AFB₁ treatment. Co-exposure of AFB₁ and ethanol escalated the activities of these serum enzymes. Administration of ethanol and AFB₁ separately resulted in significant decrease in both non-enzymatic antioxidant glutathione (GSH) level and enzymatic antioxidant catalase (CAT) and glutathione-S-transferase (GST) activities, whereas lipid peroxidation was markedly elevated. Superoxide dismutase activity and vitamin C level remained unaffected in all treatment groups. Co-exposure of animals to ethanol and AFB₁ showed additive effects on the activities of GST and CAT as well as on the GSH level. Histopathological study revealed that these compounds interact together to exacerbate their individual effects on the liver. In summary, the data presented showed that AFB₁ and ethanol co-exposure induced severe oxidative damage to the liver of mice and as such humans consuming excessive amount of ethanol and diets contaminated with AFB₁ simultaneously may be at greater risk of the hepatotoxic effects of these compounds.