Optimized renal protection with combined thymoquinone and glycine treatment: synergistic management of streptozotocin-induced nephropathy

Diabetic nephropathy is still a chief reason for morbidity and mortality in persons with renal dysfunction. Thymoquinone, a primary constituent of black seed oil extracted from Nigella sativa, has anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Glycine, an amino acid and neurotransmitter, participates in diverse physiological mechanisms. This study investigated the nephroprotective role of thymoquinone and glycine against streptozotocin (STZ)-induced diabetic nephropathy. Forty-two adult male Swiss albino rats were segregated into seven groups, each comprising six. These groups consisted of control normal rats; rats administered 60-mg STZ/kg (nephropathy); nephropathy rats treated with oral doses of 20-mg/kg/day thymoquinone (T20) or 30-mg/kg/day thymoquinone (T30); nephropathy rats treated with oral doses of 50-mg/kg/day glycine (G50) or 100-mg/kg/day glycine (G100); (T + G) nephropathy rats receiving combination therapy of 30-mg/kg/day thymoquinone and 100-mg/kg/day glycine. Various biochemical factors, including glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), total and myocardial creatine kinase (CK), kidney function parameters, blood electrolytes (Na, K, Cl, Ca, and P), and kidney histopathology, were assessed. The combined therapy of thymoquinone and glycine demonstrated enhanced efficacy in improving biochemical profiles, antioxidant levels, anti-inflammatory responses, and renal structure compared to monotherapies employing thymoquinone or glycine. The confluence of thymoquinone and glycine potentially operates through manifold pathways, encompassing the regulation of oxidative stress and modulation of inflammatory cascades. This study elucidates the potential synergistic benefits of integrating thymoquinone and glycine in diabetic nephropathy management, thereby heralding novel avenues for therapeutic interventions.