3-Indolepropionic acid prevented chlorpyrifos-induced hepatorenal toxicities in rats by improving anti-inflammatory, antioxidant, and pro-apoptotic responses and abating DNA damage.

The application of chlorpyrifos (CPF), an organophosphorus pesticide to control insects, is associated with oxidative stress and reduced quality of life in humans and animals. Indole-3-propionic acid (IPA) is a by-product of tryptophan metabolism with high antioxidant capacity and has the potential to curb CPF-mediated toxicities in the hepatorenal system of rats. It is against this background that we explored the subacute exposure of CPF and the effect of IPA in the liver and kidney of thirty rats using five cohort experimental designs (n = 6) consisting of control (corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), IPA alone (50 mg/kg), CPF + IPA1 (5 mg/kg + 25 mg/kg), and CPF + IPA2 (5 mg/kg + 50 mg/kg). Subsequently, we evaluated biomarkers of hepatorenal damage, oxidative and nitrosative stress, inflammation, DNA damage, and apoptosis by spectrophotometric and enzyme-linked immunosorbent assay methods. Our results showed that co-treatment with IPA decreased CPF-upregulated serum hepatic transaminases, creatinine, and urea; reversed CPF downregulation of SOD, CAT, GPx, GST, GSH, Trx, TRx-R, and TSH; and abated CPF upregulation of XO, MPO, RONS, and LPO. Co-treatment with IPA decreased CPF-upregulated IL-1ß and 8-OHdG levels, caspase-9 and caspase-3 activities, and increased IL-10. In addition, IPA averts CPF-induced histological changes in the liver and kidney of rats. Our results demonstrate that co-dosing CPF-exposed rats with IPA can significantly decrease CPF-induced oxidative stress, pro-inflammatory responses, DNA damage, and subsequent pro-apoptotic responses in rats' liver and kidneys. Therefore, supplementing tryptophan-derived endogenous IPA from exogenous sources may help avert toxicity occasioned by inadvertent exposure to harmful chemicals, including CPF-induced systemic perturbation of liver and kidney function.

3-Indolepropionic acid upturned male reproductive function by reducing oxido-inflammatory responses and apoptosis along the hypothalamic-pituitary-gonadal axis of adult rats exposed to chlorpyrifos.

We examined the effect of 3-Indolepropionic acid (3-IPA), an antioxidant on the organophosphorus pesticide chlorpyrifos (CPF)-induced reproductive toxicity in rats. The five experimental rat cohorts were treated per os for 14 consecutive days as follows: Control (Corn oil 2 mL/kg body weight), CPF alone (5 mg/kg), 3-IPA alone (40 mg/kg) and the co-treated rat cohorts (CPF:5 mg/kg + 3-IPA: 20 or 40 mg/kg). Biomarkers of testicular and epididymal function, oxidative stress, myeloperoxidase (MPO) activity and the levels of nitric oxide (NO), reactive oxygen and nitrogen (RONS) species and lipid peroxidation (LPO) were assessed. Also, tumour necrosis factor-alpha (TNF-α), Bcl-2-associated X (Bax) and B cell lymphoma 2 (Bcl-2) proteins were estimated, and tissue histology was microscopically examined. CPF alone significantly (p < 0.05) increased biomarkers of reproductive toxicities were averted in rats co-treated 3-IPA. Decreases in antioxidants and increases in lipid peroxidation and reactive oxygen and nitrogen species were lessened (p < 0.05) in CPF and 3-IPA co-treated rats. CPF mediated increases in TNF-α, NO, Bax, and MPO activity was reduced (p < 0.05) in the epididymis, testes, and hypothalamus of rats co-treated with 3-IPA. In addition, Bcl-2 expression was increased in rats co-treated with 3-IPA dose-dependently. Histopathological examination revealed severe lesions induced by CPF were prevented in rats co-treated with 3-IPA. Our findings demonstrate that exogenous 3-IPA reduced CPF-induced oxidative stress, inflammation, and apoptosis in the epididymis and testes of male rats.

Gallic acid protects against Aflatoxin B1 -induced oxidative and inflammatory stress damage in rats kidneys and liver.

The adverse effect of Aflatoxin B1 (AFB1 ) exposure in both humans and rodents has been widely reported. The beneficial health effects of gallic acid (GA) against AFB1 -induced toxicity in vitro have been published. Here, we present in vivo findings on AFB1 and GA on hepatorenal function in rats, exposed to AFB1 (75 µg/kg body weight) only or co-treated with GA (20 or 40 mg/kg) for 28 successive days. AFB1 significantly increased pro-inflammatory biomarkers and suppressed IL-10 levels in rats' liver and kidney. AFB1 caused increased (p < .05) oxidative stress by decreasing antioxidant enzymes levels and increasing levels of reactive oxygen and nitrogen species. Furthermore, reduction (p < .05) in cellular glutathione (GSH) levels and increased (p < .05) hepatorenal markers of toxicity were detected in rats treated with AFB1 . These observed alterations were, however, reversed in GA co-treated rats. GA ameliorated AFB1 -induced hepatorenal dysfunction by decreasing oxidative stress and inflammation in rats. PRACTICAL APPLICATIONS: GA can chemoprotect against the damaging effects of toxins contaminating food. GA is widely distributed in plants and in use in industries as antioxidant, immune-regulator, and natural defense agent against infections when consumed. Here, we disclosed that GA ameliorates AFB1 -induced hepatorenal dysfunction by suppressing oxidative stress, inflammation, and enhanced apoptosis, thus improving hepatorenal functions in rats exposed to AFB1.

Gallic acid and omega-3 fatty acids decrease inflammatory and oxidative stress in manganese-treated rats.

IMPACT STATEMENT: Humans and animals are regularly exposed to toxic chemicals with subsequent adverse effects. Manganese exposure occurs via contaminated sources; over-exposure is associated with neuronal, hepatorenal dysfunction, etc. This work advances the field of natural chemopreventive agents by reporting evidence lacking in the literature on GA and ω-3-FA obtained primarily from the diet in protecting biological beings against toxic chemicals. Individually, GA and ω-3-FA exhibit various pharmacological effects. Our findings confirm the previous reports; however, we demonstrate the additional evidence for GA and ω-3-FA in abating toxic response incumbent on oxidative damage associated with manganese exposure. These findings further underscore the relevance of GA usage in food, cosmetics-pharmaceutical industries, and ω-3-FA as a safe supplement. Dietary supplements with GA and fish oil-rich in ω-3FA may be the potential natural therapy against hepatorenal injury in individuals inadvertently or occupationally exposed to manganese, thereby, promoting human and veterinary health outcomes.

Diethylnitrosamine aggravates cadmium-induced hepatorenal oxidative damage in prepubertal rats.

The adverse health consequences of environmental, occupational, and dietary exposure to either diethylnitrosamine (DEN) or cadmium (Cd) have been widely investigated. However, because most environmental exposures to xenobiotics do not occur in isolation but in mixtures, the effects of simultaneous exposure to both DEN and Cd on hepatorenal function deserves investigation. The present study investigated the impact of 7 days oral co-exposure to 10 mg/kg body weight (b.w.) of DEN and 5 mg/kg b.w. of Cd on biomarkers of hepatic and renal functions, antioxidant defense systems, and oxidative stress indices in the liver and kidney of prepubertal rats. The results showed that the significant (p < 0.05) increases in the levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase, urea, and creatinine following separate administration of DEN and Cd to rats were further increased in the co-exposure group. Moreover, marked decreases in the activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase as well as glutathione levels following individual administration of DEN and Cd to rats were exacerbated in the co-exposure group. Further, the marked increase in the lipid peroxidation level and the histopathological lesions in the liver and kidney of rats treated with DEN or Cd alone were intensified in the co-exposure group These findings indicate that co-exposure to DEN and Cd elicited more severe hepatic and renal oxidative damage in the rats, thus suggesting a greater risk to humans who are co-exposed to them.