Effects of the Long-term Treatment of Proton Pump Inhibitors on the Function of Kidney and Liver in Laboratory Female Rats

Proton pump inhibitors (PPIs) are a group of medications effectively used to inhibit gastric acid secretion and to treat many acid-related disorders, including gastroesophageal reflux disease and other gastric disorders. Recent studies recommended that they may be associated with the risk of chronic kidney disease and liver disease. Therefore, the current study aimed to investigate the effect of long-term treatment with PPIs on kidney and liver function in laboratory rats. Fifteen female albino white rats (Rattusnorvigicus) were randomly assigned to three groups of five animals. The control group was fed regular pellet, group PPI-2 received standard pellet diet and was given esomeprazole (10 mg/kg b.w.) via daily oral gavage in mornings for two weeks, and group PPI-3 was fed standard pellet diet and was given esomeprazole (10 mg/kg b.w.) via daily oral gavage in mornings for three months. Blood samples were taken after 2 weeks and 3 months by cardiac puncture for measuring serum creatinine, urea, total bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). In addition, kidney and liver tissues were histopathologically evaluated. Serum creatinine, urea, ALT, total bilirubin, and ALP significantly increased in group PPI-3, compared to other groups. Histopathological study of the kidneys and liver revealed normal histology structure in the control group and the rats of the PPI-2 group, while some histological changes were observed in the liver and kidney of the animals in the PPI-3 group. The histological changes included the widening of Bowman's space and shrunken glomeruli, whereas the renal tubules had congested tubular cells. Furthermore, congestion in the blood vessels and hepatic cells degradation were observed in the liver. These data indicate that the long-term administration of PPIs has adverse effects on the structure and function of the kidney and liver.