The ameliorative effect of curcumin on hepatic CYP1A1 and CYP1A2 genes dysregulation and hepatorenal damage induced by fenitrothion oral intoxication in male rats.

This research aimed to assess curcumin (CUR) effects on fenitrothion (FNT), a broad-spectrum organophosphate insecticide, -induced hepatorenal damage. Thirty adult male Wistar rats were allocated at random to five equal groups orally administered distilled water containing 1% carboxyl methylcellulose, corn oil (1 mL/rat), CUR (100 mg/kg b.wt.), FNT (5 mg/kg b.wt.), or CUR + FNT. CUR and FNT were dosed three times a week for two months. At the end of this trial, blood and tissue samples (liver and kidney) were subjected to molecular, biochemical, and histopathological assessments. The results revealed that CUR significantly diminished the FNT-induced up-regulation of hepatic CYP1A1 and CYP1A2 transcriptional levels. Moreover, CUR significantly suppressed the increment of the serum levels of hepatic alanine aminotransferase, gamma-glutamyl transferase, and kidney damage indicators (urea and creatinine) in FNT-intoxicated rats. Furthermore, in the hepatic and renal tissues, CUR remarkably restored the FNT-associated depletion of the antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione S transferase, catalase, and superoxide dismutase). In addition, CUR notably reduced the FNT-induced increment in malondialdehyde content in the hepatic and renal tissues. Besides, the pathological aberrations in liver and kidney tissues resulting from FNT exposure were significantly abolished in FNT + CUR treated rats. Overall, CUR could be an effective ameliorative agent against negative pesticide impacts like FNT.

Taurine and hesperidin rescues carbon tetrachloride-triggered testicular and kidney damage in rats via modulating oxidative stress and inflammation.

AIMS: This study assessed the prophylactic or therapeutic effects of taurine (TR) and/or hesperidin (HES) on carbon tetrachloride (CCl4) induced acute kidney and testicular injury in rats. MAIN METHODS: Rats were randomly divided into nine experimental groups including control; corn oil; CCl4; HES/CCl4; TR/CCl4; HES + TR/CCl4; CCl4/HES; CCl4/TR; and CCl4/HES + TR groups. CCl4 was intraperitoneally injected with a single dose of 2 ml /kg b.w. HES and TR were orally gavaged twice weekly 100 mg/kg b.w. for four weeks. Kidney function, inflammatory response, sexual hormones, and oxidative stress indicators were assessed. Histomorphological and immune-histochemical studies of the inflammatory marker nuclear factor kappa (NF-κB) in renal and testicular tissues were performed. KEY FINDINGS: The results showed that the TR and/or HES treatment significantly suppressed CCl4 induced rise of urea, uric acid, potassium, and follicle-stimulating hormone levels. However, significant restoration of sodium, testosterone, and luteinizing hormone was apparent in CCl4 exposed rats received HES and/or TR. Also, the HES and/or TR treatment significantly rescues CCl4 induced oxidative stress and inflammation. Moreover, the HES and/or TR dosing significantly repaired the CCl4 evoked altered renal and testicular architecture and suppressed NF-κB immunoexpression. Notably, alleviating CCl4 induced renal and testicular damage was more effective in the prophylactic groups than the therapeutic groups. Also, most of the estimated parameters of the HES + TR group did not significantly vary from those of single TR or HES. SIGNIFICANCE: In conclusion, HES or TR could efficiently guard against CCl4 nephro-and reprotoxic effects, but both bioactive combinations afford only a limited synergistic outcome.

Single or combined protective and therapeutic impact of taurine and hesperidin on carbon tetrachloride-induced acute hepatic injury in rat.

Currently, hepatic injury due to environmental pollutants extremely threatens human health and elicits great concern. Hence, there is a high global interest to find natural novel formulation products with potent hepatoprotective activity to combat liver disease. Hence, we evaluated the protective or therapeutic effect of hesperidin (HSP) and taurine (TAU), individually and in combination, on carbon tetrachloride (CCl4)-induced acute hepatic injury in rats. The pre- or posttreatment by HSP and/or TAU significantly depressed CCl4-induced elevation of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, gamma-glutamyl transferase, total bilirubin, direct bilirubin, indirect bilirubin, malondialdehyde, globulins (α1, α2, ß, and γ), albumin/globulin ratio, triglycerides, total cholesterol, high-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, nitric oxide, and myeloperoxidase levels. Also, the pre- or posttreatment by HSP and/or TAU significantly minimized CCl4-induced reduction of superoxide dismutase, catalase, reduced glutathione, and albumin concentrations. Furthermore, the protective or therapeutic administration of HSP and/or TAU markedly restored the CCl4-induced altered hepatic architecture, depleted glycogen, and DNA contents. Notably, alleviating CCl4-induced hepatotoxicity was more prominent in the protective groups than the therapeutic groups. More importantly, most of biochemical and histopathological parameters of HSP+TAU did not significantly differ from those of separate TAU or HSP neither before nor after CCl4 exposure. Conclusively, HSP or TAU could be candidate protective agents against CCl4 hepatotoxic impacts but the combination of both bioactive offers only a limited synergistic effect. Graphical abstract.

Downregulation of male-specific cytochrome P450 by profenofos.

The health hazards of individual organophosphorus insecticides have been characterized by their acute toxicity, mainly by investigating their cholinesterase inhibition. However, the chronic effects of most of these toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an organophosphorus pesticide widely used in cotton cultivation. In the present study, we investigated the effect of profenofos on male-specific cytochrome P450 (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls. Overall, the present study suggests that profenofos acts as an endocrine disruptor of male-specific CYP enzymes and affects testosterone concentration, which implicates its deleterious effects on animal or human males chronically exposed to organophosphorus pesticide.