Abstract

Nephrotoxicity, defined as structural and functional impairment of the kidneys due to chemical, biological, or 
metabolic insults, is a significant contributor to global morbidity and mortality. It arises from diverse causes 
including pharmaceutical agents, heavy metals, environmental toxins, infectious diseases, and metabolic conditions 
such as diabetes and hypertension. Pathophysiological mechanisms involve oxidative stress, mitochondrial 
dysfunction, inflammation, dysregulation of renal hemodynamics, and apoptosis/necrosis of tubular cells. Herbal 
medicines have been investigated both as protective interventions and, paradoxically, as causative agents of 
nephrotoxicity. Numerous phytochemicals-such as polyphenols, flavonoids, alkaloids, terpenoids, and saponins
exhibit antioxidative, anti-inflammatory, and cytoprotective activities, which may counter renal injury by 
modulating signaling pathways (Nrf2, NF-κB, TGF-β/Smad). Prominent candidates include curcumin, resveratrol, 
silymarin, quercetin, and berberine, as well as complex formulations from Ayurvedic, Chinese, and African 
traditional medicine. However, nephrotoxic risks arise from intrinsic phytochemical toxicity (e.g., aristolochic acids), 
adulteration with heavy metals, contamination, or herb-drug interactions. The duality of herbal remedies as potential 
nephroprotectants and nephrotoxins demands rigorous mechanistic research, standardized preparations, and long
term clinical trials. This review synthesizes current evidence on nephrotoxicity mechanisms, the protective role of 
herbal interventions, and the safety concerns critical to clinical translation.