Protective effects of coenzyme Q10 and Pluchea lanceolata against proton pump inhibitor-induced nephrotoxicity: Biochemical, histological, and ultrastructural evaluation.

OBJECTIVE

Proton pump inhibitors (PPIs) are widely used to reduce gastric acid secretion. However, prolonged use has been associated with nephrotoxicity that necessitates protective agent's administration to mitigate these harmful effects. The present study aims to evaluate the potential protective effects of Coenzyme Q10(CoQ10), mitochondrial antioxidant, along with natural plant extracts, Pluchea lanceolata (PL) that possess antioxidant properties, against nephrotoxicity, renal damage, and apoptosis in renal tissue induced by prolonged exposure to PPIs.

METHODS

Forty-eight male rats were divided into six equal groups: control group received distilled water; esomeprazole group received esomeprazole (5 mg/kg/day); Pluchea lanceolata group received PL extract (400 mg/kg/day); PL+esomeprazole group received both PL and esomeprazole; CoQ10 group received coenzyme Q10 (10 mg/kg/day); and CoQ10 +esomeprazole group received both CoQ10 and esomeprazole. All treatments were administered for four weeks. At the end, blood and urine samples were collected for measurement of serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (e-GFR), urinary creatinine, and microalbuminuria. Kidney tissues were processed for the analysis of total oxidative stress (TOS) and total antioxidant capacity (TAC). Additional kidney samples were collected for histopathological examination, immunohistochemical analysis of caspase-3 expression, and ultrastructural evaluation using electron microscopy.

RESULTS

Esomeprazole administration resulted in a significant increase in serum creatinine, urea, and albumin-creatinine ratio, along with a reduction in e-GFR and TAC. Histologically, esomeprazole significantly decreased glomerular count and proximal tubule diameter and increased the overall histopathological score. Immunohistochemical analysis showed strong positive expression of caspase-3 in the esomeprazole group, indicating enhanced apoptotic activity. Electron microscopy revealed marked structural alterations, including distorted brush borders, mitochondrial swelling, and podocyte vacuolations. Notably, these renal tissue alterations were markedly alleviated in the groups that received coenzyme Q10 and/or PL.

CONCLUSION

Esomeprazole induces significant renal toxicity, primarily through structural damage and oxidative stress mechanisms. Coenzyme Q10 exhibited strong protective effects by enhancing antioxidant defenses, while PL provided moderate renal protection.