Zinc sulphate attenuates metabolic dysfunctions induced by olanzapine via the reduction of insulin resistance, hepatic oxidative stress, and inflammation in albino rats

Olanzapine, an atypical antipsychotic drug, is used to treat psychological diseases. However, it's use carries common side effects. Those include weight gain, dyslipidemia, elevated glucose levels, and disrupted oxidative balance. We aimed to test the effect of zinc coadministration to lessen metabolic disturbances, inflammation and oxidative stress in a rat model. Four treatment groups (n = 6) were involved in this investigation. Group 1 was the control group (received no intervention). Group 2 received olanzapine (10 mg/kg, p.o.; daily) for six weeks, whereas Groups 3 and 4 received 50 mg/kg and 100 mg/kg of zinc sulphate (ZnSO₄,p.o.; daily) respectively, in addition to olanzapine (10 mg/kg p.o.; daily). Following treatment completion, group 2 showed increased levels of stress markers (GSSG, MDA, and NO) and impaired levels of antioxidant markers (CAT, SOD, and GSH). Further, a strong positive correlation between insulin resistance index (HOMA-IR) and IL-6, TNF-α, and MDA of liver. Insulin resistance is a possible manifestation of the oxidative stress burden and the widespread inflammatory environment. In groups 3 and 4, however, ZnSO₄ recovered each of these markers in a dose-dependent manner. Improvements were also noted in other homeostatic markers, such as taurine, coenzyme Q10, ascorbic acid, and vitamin E. Remarkably, in both combination groups, there was a significant improvement in all metabolic indicators of dyslipidemia (triglycerides, total cholesterol) and insulin resistance index. The biochemical study and the histological assessment of the liver slices agreed with the results. Thus, the results clearly suggest that Zinc supplementation can significantly improve oxidative stress, inflammation, metabolic perturbation (dyslipidemia and insulin resistance), and liver injury caused by olanzapine in Albino rats.