Ameliorative Effect Of Thiamine Pyrophosphate Against Cisplatin-Induced Reproductive System Damage Within Male Rats

Abstract

Maitham Abd Ali Mnati, Bahir Abdul Razzaq Mshimesh, Mustafa Mohammed Ibraheem, Suzan Yousif Jasim

Background: Cisplatin considers one of the most potent antineoplastic drugs that manage solid and germ cell cancer. The major drawback in cisplatin treatment is infertility. Thiamine pyrophosphate is the active form of thiamine which has an important role in the oxidative phosphorylation pathway.
Objective: This study aimed to evaluate the protective effect of thiamine pyrophosphate on the testes of male rats exposed to a single dose of cisplatin.
Methods: Twenty-eight albino rats were randomly grouped into four groups. Negative control group: received normal saline, Positive control group: received normal saline and cisplatin, Low-dose thiamine pyrophosphate group: received thiamine pyrophosphate (50 mg/kg) and cisplatin, High- dose thiamine pyrophosphate group: as above but thiamine pyrophosphate dose was 100 mg/kg. Semen samples used to measure the sperms motility, and concentration. Serum samples were gathered to measure the levels of Testosterone. Testicular samples were collected to determine testicular superoxide dismutase, glutathione peroxidase, and caspase-3 levels. The testes were harvested to achieve histopathological study and testicular prostaglandin F2α expression.
Results: Testicular gonadosomatic index, sperm motility and concentration, testosterone and antioxidant markers levels within testicular tissue were significantly decreased within positive control group (received just cisplatin) compared with the negative control, while co-treatment with thiamine pyrophosphate can significantly improve these parameters in a dose-dependent manner. Conversely, the testicular caspase-3 level was elevated markedly in the cisplatin alone group while reduced significantly in a dose-dependent manner when thiamine pyrophosphate was co-administered. In the cisplatin group, histopathological study demonstrated a marked alteration in the structure of testicular tissue while under immunohistochemical staining, the testicular prostaglandin F2α expression was significantly overexpressed, whereas co-treatment with thiamine pyrophosphate can significantly reduce this up-regulation and reverse histopathological findings.
Conclusion: Thiamine pyrophosphate may act as a protective agent that ameliorates rat’s testicular damage induced by cisplatin treatment in a dose-dependent manner. The suggested mechanism may attribute to its antioxidant and anti-apoptotic action.