Dose and time-dependent toxicological impact of pantoprazole on vascular endothelium and renal tissue. (15th October 2020)

• Record Type: Journal Article
• Authors: Taneja, Gaurav; Thanikachalam, Punniyakoti V.; Rajput, Satyendra K.
• Is Part Of: Toxicology letters. Volume 333(2020)
• Page Start: 97
• Page End: 104
• Publication Date: 2020-10-15
• Subjects: Nitric oxide -- Pantoprazole -- Proton pump inhibitors -- Renal abnormalities -- Toxicology -- Vascular endothelial dysfunction; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.07.031
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: Pantoprazole could not be safe as assumed blindly. Acute treatment of pantoprazole may be safe even at higher dose. Chronic use of pantoprazole may cause toxicity on endothelium and renal tissue. Toxic impact in chronic treatment is corresponding dose of pantoprazole. Toxicity of pantoprazole is endorsed by oxidative stress and reduced NO level. Abstract: Proton pump inhibitors (PPIs) have wide pleiotropic action in addition to their therapeutic potential in gastroesophageal reflux diseases. Conversely, recent reports revealed a significant incidence of toxic events of PPIs including nephritis, osteoporosis, and cardiac damage. Thus, the study was designed to reconcile the deceptive contraindications. The present investigation targeted to reveal the toxic impact of sub-acute and sub-chronic administration of pantoprazole (PPZ) with different concentrations (low dose 4 mg/kg, medium-dose 8 mg/kg and high dose 16 mg/kg once a day) on normal vascular endothelium and renal tissue of rats. Vascular endothelial dysfunction (VED) was estimated by the contractility of an isolated aortic ring, nitrite/nitrate concentration, oxidative stress, and integrity of the endothelium layer. Moreover, the renal abnormalities were further confirmed by an increased level of serum creatinine, blood urea nitrogen (BUN), the incidence of microproteinuria, and structural alteration. Sub-acute administration of PPZ treatment did not produce any toxicological impact on endothelium and renal tissue. Whereas, sub-chronic administration of PPZ treatment causes moderate VED and renal dysfunction in a dose-dependent manner. Sub-chronic treatment of PPZ also influences the mitigation of NO and elevation of oxidative stress. Collecting all the evidence, it concludes that decreased nitric oxide availability and increased levels of oxidative stress may be a possible underlying mechanism of causing VED and renal abnormalities from high-dose PPZ treatment.