Coenzyme Q10, Biochanin A and Phloretin Attenuate Cr(VI)-Induced Oxidative Stress and DNA Damage by Stimulating Nrf2/HO-1 Pathway in the Experimental Model.

Hexavalent chromium [Cr(VI)] has emerged as a prevailing environmental and occupational contaminant over the past few decades. However, the knowledge is sparse regarding Cr(VI)-induced neurological aberrations, and its remediation through natural bioactive compounds has not been fully explored. This study intended to probe the possible invigorative effects of nutraceuticals such as coenzyme Q10 (CoQ10), biochanin A (BCA), and phloretin (PHL) on Cr(VI) intoxicated Swiss albino mice with special emphasis on Nrf2/HO-1/NQO1 gene expressions. Mice received potassium dichromate (75 ppm) through drinking water and were simultaneously co-treated intraperitoneally with CoQ10 (10 mg/kg), BCA, and PHL (50 mg/kg) each for 30-day treatment period. The statistics highlight the elevated levels of lipid peroxidation (LPO) and protein carbonyl content (PCC) with a concomitant reduction in the superoxide dismutase (SOD), glutathione-S-transferase (GST), reduced glutathione (GSH), total thiols (TT), catalase (CAT), and cholinesterase activities in the Cr(VI)-exposed mice. The collateral assessment of DNA fragmentation, DNA breakages, and induced histological alterations was in conformity with the above findings in conjugation with the dysregulation in the Nrf2 and associated downstream HO-1 and NQO1 gene expressions. Co-treatment with the selected natural compounds reversed the above-altered parameters significantly, thereby bringing cellular homeostasis in alleviating the Cr(VI)-induced conciliated impairments. Our study demonstrated that the combination of different bioactive compounds shields the brain better against Cr(VI)-induced neurotoxicity by revoking the oxidative stress-associated manifestations. These compounds may represent a new potential combination therapy due to their ability to modulate the cellular antioxidant responses by upregulating the Nrf2/HO-1/NQO1 signaling pathway against Cr(VI)-exposed population. HIGHLIGHTS: Cr(VI)-associated heavy metal exposure poses a significant threat to the environment, especially to living organisms. Cr(VI) exposure for 30 days resulted in the free radical's generation that caused neurotoxicity in the Swiss albino mice. Natural compounds such as coenzyme Q10, biochanin A, and phloretin counteracted the neurotoxic effect due to Cr(VI) exposure in scavenging of free radicals by enhancing Nrf2/HO-1/NQO1 gene expressions in maintaining the cellular homeostasis.

Therapeutic effects of CoenzymeQ10, Biochanin A and Phloretin against arsenic and chromium induced oxidative stress in mouse (Mus musculus) brain.

Arsenic and chromium are the most common environmental toxicants prevailing in nature. Hence, the present study endeavors to investigate the salutary effects of Coenzyme Q10 (CoQ10), Biochanin A (BCA), and Phloretin (PHL) on the combined neurotoxic impact of arsenic and chromium in the Swiss albino mice (Mus musculus). Sodium meta-arsenite (100 ppm) and potassium dichromate (75 ppm) were given orally in conjugation with CoQ10 (10 mg/kg), BCA & PHL (50 mg/kg each) in accordance with body weight per day for the 2 weeks experimental duration. Weight reduction was figured out in the exposed toxic group of arsenic and chromium in contrast with the comparison group (control), and with the selected anti-oxidants treatment, it rose significantly to the basal status (p < 0.05). The concentration of arsenic and chromium was reduced significantly (p < 0.001) amidst all the natural compounds co-medicated groups. Anti-oxidant indicators, viz. lipid peroxidation (LPO) and protein carbonyl content (PCC), were found elevated, with reduction observed in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), glutathione s-transferase (GST), and total thiols (TT) in the arsenic and chromium, co-exposed mice. The alterations in redox homeostasis were well corroborated with the estimations of cholinesterase's enzymes (p < 0.05) along with DNA fragmentation assay and altered Nrf2 signaling. The administration of CoQ10, BCA, and PHL ameliorated the effects of arsenic and chromium induced oxidative stress in the exposed mice. Our research unfolds the remedial outcome of these natural compounds contrary to the combined arsenic and chromium associated-neurotoxicity in the experimental model.

Therapeutic effects of biochanin A, phloretin, and epigallocatechin-3-gallate in reducing oxidative stress in arsenic-intoxicated mice.

One of the most common toxicant prevailing in our environment is the arsenic. The present study is an attempt to investigate the effects of some of the common flavonoids, such as biochanin A (BCA), phloretin, and epigallocatechin-3-gallate (EGCG), on arsenic toxicity in the Swiss albino mice. For this purpose, mice were orally treated with sodium meta-arsenite (20 mg/kg bw/day), along with co-administration of BCA (50 mg/kg bw/day), phloretin (50 mg/kg bw/day), and EGCG (40 mg/kg bw/day) for the 2-week duration. All the mice were euthanized at the end of the treatment period, and the observations were made in the following parameters. Arsenic reduced the sperm motility as compared with the control (p < 0.05) and was restored back to the normal status with the flavonoids treatment significantly (p < 0.05). The arsenic concentrations in the kidney and liver tissues were found significantly reduced with all the flavonoids co-treatment (p < 0.001). There was a reduction in the levels of superoxide dismutase (SOD), reduced glutathione (GSH), and glutathione S-transferase (GST) antioxidant markers, with the increased lipid peroxidation (LPO), protein carbonyl content (PCC), and catalase (CAT) levels in the arsenic-intoxicated mice performed in the different tissues. The biochemical homeostasis alterations were well correlated with the estimations of cholinesterase enzyme levels in the brain tissues (p < 0.05) along with DNA damage analysis (Comet) carried out in the blood cells (p < 0.05). These above results are well corroborated with the histopathological findings performed in the brain tissue, along with the increased upregulation seen in the Nrf2 signalling, with all the flavonoid co-treatment carried in the kidney tissue. The administration of BCA, phloretin, and EGCG, in a major way, reversed the alterations in the abovementioned parameters in the arsenic-intoxicated mice. Our findings revealed the beneficial effects of the flavonoids against the arsenic-induced toxicity, due to their ability to enhance the intracellular antioxidant response system by modulating the Nrf2 signaling pathway.