Tert-butylhydroquinone abrogates fructose-induced insulin resistance in rats via mitigation of oxidant stress, NFkB-mediated inflammation in the liver but not the skeletal muscle of high fructose drinking rats.

The effect of 21% fructose drinking water (FDW) (w/v) on some parameters of metabolic syndrome, hepatic, and skeletal muscular histology of rats was studied using standard techniques. Twenty male albino rats were divided into four groups of 5 rats each in this in vivo study. Group I received distilled water, group 2 received FDW, group 3 received FDW and metformin (300 mg/kg body weight daily, orally), group 4 received FDW and 1% tert-butylhydroquinone feed. FDW changed the serum leptin, triacylglycerol, very low-density lipoprotein, and C-reactive protein levels of the rats, inducing hypertriglyceridemia, oxidative stress, and inflammation in their liver (but not the skeletal muscle) and insulin resistance which were modulated with metformin and tBHQ as corroborated by liver and muscle histology. The study reveals the potentials of metformin and tBHQ in mitigating hepatic and skeletal muscular morphological changes arising from exposure to high fructose drinks. PRACTICAL APPLICATIONS: There has been an increase in the global consumption of fructose (either as a sweetner in beverages or soft and carbonated drinks) in the last few decades and this has been positively correlated with the global increase in metabolic complications. Regular intake of fructose contributes to the pathogenesis of lipid disorders, oxidant stress, and chronic inflammation, which are linked with the metabolic syndrome components (MetS) (obesity, insulin resistance, and cardiovascular diseases) as well as increased morbidity and mortality. Given that the approaches that have been applied to treat the MetS have not been able to totally arrest it, currenty study which showed that tBHQ abrogated fructose-induced insulin resistance, dyslipidemia, hepatic, and skeletal muscular pathology in the rats places tBHQ in the spotlight as a nutraceutical that could be of relevance in mitigating high dietary fructose-induced hepatic and skeletal muscular pathology.

Abatement of cyclophosphamide-induced splenic immunosuppressive indoleamine 2, 3-dioxygenase and altered hematological indices in Wister rats by dietary quercetin.

The immunotoxicity mediated by cyclophosphamide (CYP) was earlier reported. Quercetin, due to its anti-oxidative/inflammatory properties elicits a plethora of health benefits. However, the influence of quercetin on the splenic/immunotoxicity linked with CYP-induced indoleamine 2,3-dioxygenase (IDO) is unavailable in the literature. We investigated the effects of quercetin on the splenic immunosuppressive IDO and hematological indices of immune response in rats. Animals were treated with CYP (100 mg/kg) alone or co-treated (CYP + quercetin [100 mg/kg + 50 mg/kg respectively]) at days 1, 3, 5, and 7. Results revealed that CYP treatment alone significantly provoked an oxidative-inflammatory response, increased serum kynurenine concentration, and concomitantly increased immunosuppressive IDO and tryptophan 2, 3-dioxygenase (TDO), in the spleen as well as altering hematological indices. Quercetin co-treatment enhanced activities of antioxidant enzymes, inhibited myeloperoxidase (MPO) activity, lowered levels of nitric oxide, interferon-Υ (IFN-Υ), and interleukin-6 (IL-6), and reduced kynurenine concentration as well as IDO/TDO activities. Quercetin co-treatment augmented white blood cell (WBC), CD4-T cells, and other hematological indices of the immune response. In conclusion, quercetin prevented CYP-induced alterations in immune response in rats by lowering the activities of immunosuppressive IDO and TDO, inhibiting oxidative-inflammatory stress, diminution of kynurenine concentrations, and augmenting hematological parameters.

Cyclophosphamide instigated hepatic-renal oxidative/inflammatory stress aggravates immunosuppressive indoleamine 2,3-dioxygenase in male rats: Abatement by quercetin.

The hepatic-renal toxicity associated with cyclophosphamide (CYP) treatment in both animals and humans have been reported. Quercetin, a dietary flavonoid, is known to elicit beneficial health effects. However, the influence of quercetin on the hepatic-renal toxicity associated with CYP-instigated indoleamine 2,3-dioxygenase is unavailable in the literature. The current study evaluated the effects of quercetin on the dysfunctional hepatic-renal status triggered by CYP exposure in rats. Experimental animals were exposed to CYP (100 mg/kg) or co-treated with quercetin (50 mg/kg) every other day for 7 days. Results revealed that quercetin treatment significantly assuaged CYP-mediated oxidative-inflammatory response, as well as augmenting serum levels of thyroid hormones. Additionally, quercetin attenuated CYP-induced reduction in antioxidant enzyme activities and enhanced hepatic-renal function markers, namely aspartate aminotransferase (AST), alanine aminotransferase (ALT), Alkaline phosphatase (ALP), and levels of urea and creatinine. Quercetin efficiently mitigated CYP-mediated increase in myeloperoxidase (MPO) activity, levels of nitric oxide and interleukin-6 (IL-6) in liver and kidney of rats. CYP-induced increase in the activities of immunosuppressive indoleamine 2, 3-dioxygenase (IDO) and tryptophan 2, 3-dioxygenase (TDO) in the tissues was abated in quercetin co-treated rats. In conclusion, Quercetin ameliorated deficits in the hepatic-renal function in CYP-exposed rats by lowering the activities/expression of immunosuppressive IDO and TDO via diminution of oxidative-inflammatory stress.