Effect of thiamine pyrophosphate on cyclophosphamide-induced oxidative ovarian damage and reproductive dysfunction in female rats

Abstract

Background. Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. Thiamine pyrophosphate (TPP) to be investigated for its effect on cyclophosphamide-induced ovarian damage and reproductive dysfunction in the present study is the active metabolite of thiamine. It has been shown that TPP protects organs and tissues from oxidative stress and proinflammatory cytokine damage. Objectives.To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats. Materials and methods.Albino Wistar type female rats were divided into healthy control (HG), cyclophosphamide (CYC) and TPP + cyclophosphamide (TPPC) groups (for each group, n = 12). Thiamine pyrophosphate at a dose of 25 mg/kg was injected intraperitoneally (ip.) in the TPPC group, and 0.9% NaCI solution was injected ip. in the CYC and HG groups. One hour after the injection, 75 mg/kg of cyclophosphamide was administered ip. in the TPPC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, 6 rats from each group were euthanized with a high dose of anesthetic (50 mg/kg of sodium thiopental). Biochemical and histopathological examinations were performed on the extracted ovarian tissue. The remaining animals were kept in the laboratory with mature male rats for 2 months for reproduction.Results. Thiamine pyrophosphate significantly decreased the cyclophosphamide-induced increase in the levels of the oxidant parameter malondialdehyde (MDA), proinflammatory nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1β). In addition, TPP decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility. Conclusions.Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.

Lyophilized Equine Platelet-Rich Plasma (L-GF equina ) Antagonize the Reproductive Toxicity and Oxidative Stress Induced by Cyclophosphamide in Female Rats

“…In the uterus, epithelial degeneration, vacuoles within the epithelial lining, decreased glandular proliferation, and increased stromal brous tissue. Similar results were previously reported in rats [18,31] and mice [32]. This side effect of CP is linked to the follicle atresia and granulosa cell apoptosis [33].…”

Effect of Thiamine Pyrophosphate Upon Oxidative Brain Injury Induced by Ischemia-Reperfusion in Rats

“…MDA and MPO analysis: The MDA measurements were made according to the method described by Ozer et al 14 The absorbance of the pink complex formed by thiobarbituric acid and MDA was measured spectrophotometrically. For MPO analysis, potassium phosphate buffer (pH = 6) containing 0.5% HDTMAB (0.5% hexadecyltrimethyl ammonium bromide) was prepared from tissue homogenates and centrifuged for 15 min (+4EC, 10000 rpm).…”

“…TPP was the best indicator specifying the activity level of thiamine 10 and formed by the phosphating of thiamine in the liver with thiamine pyrophosphokinase 11 . It has been stated in numerous experimental studies that TPP protected the ovary, peripheral nerve, eye, heart and brain tissue from oxidative stress [11][12][13][14][15] . This information suggests that TPP may protect brain tissue from oxidative I/R damage.…”

Effect of thiamine pyrophosphate on oxidative damage in the brain and heart of rats with experimentally induced occlusion of the common carotid artery.

“…TPP, the active metabolite of thiamine 15 , is synthesized in the liver through the phosphorylation of thiamine by thiamine pyrophosphokinase 16 . Existing literature suggests that TPP exerts a protective effect by inhibiting the increase in oxidant and pro-inflammatory parameters 17 . Furthermore, TPP protects cardiac tissue from oxidative damage 18 .…”