Curcumin and quercetin synergistically attenuate subacute diazinon-induced inflammation and oxidative neurohepatic damage, and acetylcholinesterase inhibition in albino rats

Abstract

The ubiquitous use of diazinon (DZN, an organophosphorus insecticide) has increased the probability of occupational, public, and the ecosystem exposure; these exposures are linked to negative health outcomes. The flavonoids curcumin (CUR) and quercetin (QUE) exert significant anti-inflammatory and antioxidant activities against toxicants, including insecticides. However, it is unclear whether their combination enhances these activities. Therefore, 40 albino rat were divided randomly into the CTR, DZN, CUR + DZN, QUE + DZN, and CUR + QUE + DZN groups, which are treated daily via gavage for 28 days. DZN induced neurohepatic inflammation and oxidative damage, which was confirmed by significant (P < 0.05) induction of aspartate and alanine aminotransferases, alkaline phosphatase, lactate dehydrogenase, γ-glutamyl transferase, and tumor necrosis factor-α and inhibition of acetylcholinesterase activity. Furthermore, the liver and brain of DZN-exposed rats exhibited a notable elevation in MDA level paralleled with reduction in antioxidant molecules, i.e., glutathione, superoxide dismutase, glutathione peroxidase, and catalase. The pretreatment of DZN-intoxicated rats with CUR or QUE substantially mitigated neurohepatic dysfunction and inflammation and improved liver and brain antioxidant status with reducing oxidative stress levels. Furthermore, pretreatment with CUR + QUE synergistically restored the neurohepatic dysfunction and oxidative levels to approximately normal levels. The overall results suggested that CUR or QUE inhibits DZN-mediated neurohepatic toxicity via their favorable anti-inflammatory, antioxidant, and free radical-scavenging activities. Moreover, both QUE and CUR may be mutual adjuvant agents against oxidative stress neurohepatic damages.