Rhubarb water extract as a promising gastroprotective agent in Tamoxifen induced parietal cell damage in female rats: a histological study

Tamoxifen (TAM) is one of the most used drugs in the prevention and treatment of breast cancer. A set of common side effects was recorded associating its prolonged clinical use that ranges 3-10 years. This study aimed to investigate TAM-induced parietal cells (PCs) injury in rats and the possible protective effect of rhubarb (Rh) water extract (WE). Twenty-four adult female rats were distributed as: control group, TAM-group (3 mg/kg/day TAM for 4-weeks) and TAM+Rh-group (combined 3 mg/kg/day TAM and 20 mg/kg Rh-WE for 4-weeks). Blood sample before euthanizing rats was tested for vitamin-B12. PCs in stomach fundus were examined using histological and transmission electron microscopic studies, besides immunohistochemistry for Caspase-3, proliferating cell nuclear antigen (PCNA) and hydrogen potassium (H⁺/K⁺)-ATPase. Gastric homogenates were inspected for malondialdehyde (MDA) by ELISA. TAM intake induced structural and ultrastructural alteration in rat PCs including ballooning degeneration, apoptosis, decreased canaliculi, increased tubulovesicular system and irregular-shaped mitochondria. A significant increase of Caspase-3 immunostaining and MDA expression in gastric tissue was associated with a significant decrease of PCNA and H⁺/K⁺-ATPase-immunostaining and in serum vitamin-B12 as compared to the control group. Combined oral intake of TAM and Rh-WE revealed a significant reversal of the previous findings. Conclusion: Prolonged use of oral TAM substantially affected the structure and function of gastric PCs which can be ameliorated by Rh-WE.