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. To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats. 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. 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. Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.

Evaluating biochemically and histopathologically the effects of taxifolin on methotrexate-induced oral mucosal damage in rats. In the taxifolin+MTX (TMTX) group, 50 mg/kg taxifolin was orally administered to rats by gavage. In the MTX and healthy (HG) groups, normal saline was applied to rats as solvent by the same method. One hour after administration of taxifolin and solvent, 5 mg/kg MTX was orally administered to rats in the MTX and TMTX groups. Taxifolin and methotrexate were administered once a day for 30 days. Macroscopic, biochemical, and histopathological evaluations were performed on the inner cheek and tongue tissues of rats. These parts were removed after rats were killed with a high-dose anesthesia. Taxifolin with MTX prevented the increase in oxidant and pro-inflammatory parameters, such as malondialdehyde (MDA), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), on the inner cheek and tongue tissues of rats. Moreover, taxifolin antagonized the decrease in total glutathione (tGSH). Taxifolin decreased MTX-induced histopathological damage. These findings suggest that taxifolin may be useful to treat MTX-associated oral mucositis.

In the literature, it has been suggested that ketamine-related oxidative organ damage results from increased blood adrenaline level, and thiopental-related oxidative damage is caused by decreased adrenaline level, suggesting that ketamine-thiopental combination (KT) may be beneficial in reducing the hepatotoxic effect of ketamine. To biochemically investigate the effects of ketamine, thiopental and KT on the liver in rats. Male albino Wistar type rats received intraperitoneally (ip.) 30 mg/kg ketamine in the ketamine alone (KG) group (n = 6), 15 mg/kg thiopental in the thiopental alone (TG) group (n = 6), and 30 mg/kg ketamine + 15 mg/kg thiopental in the ketamine+thiopental (KTG) group (n = 6). The same volume of distilled water as solvent was given to the healthy (HG) animal group. This procedure was repeated once daily for 30 days. At the end of this period, the animals were killed by decapitation and their livers were removed. In liver tissue, malondialdehyde (MDA), total glutathione (tGSH), total oxidant status (TOS), total antioxidant status (TAS), tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and interleukin-6 (IL-6) levels were measured. The IL-1β, IL-6, TNF-α, adrenalin (ADR), noradrenalin (NDR), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels were determined in blood samples taken from the tail veins. In the group treated with ketamine and thiopental alone, MDA, TOS, IL-1β, IL-6, TNF-α, ADR, NDR, ALT, and AST levels were found to be high, and those of tGSH and TAS to be low. However, there was no significant change in the levels of these parameters in the KTG. These results indicate that oxidative stress and inflammation developed in the liver tissue of the group that used ketamine and thiopental alone, suggesting that the KT form may be safer in terms of toxicity in the clinical usage.

Inflammation, oxidative damage, and adenosine triphosphate (ATP) depletion play a role in the pathogenesis of cisplatin (CIS)-induced oral mucositis. Objective: The purpose of this research is to examine the impact of ATP against potential oral mucositis development in cisplatin-treated rats. Methodology All rats were randomly assigned to four groups, namely healthy control group (HG), ATP group (ATPG), Cisplatin group (CISG), and ATP + Cisplatin group (ATCS). Firstly, ATP 4 mg/kg was administered via intraperitoneal injection (IP) to both ATPG and ATCS groups. The same volume of normal saline was injected into HG and CISG groups. After 1 h, cisplatin 5 mg/kg was administered via IP to CISG and ATCS groups. The drugs were taken 1x1 for 7 d. Later, tongue tissues were collected from all groups. Biochemical, macroscopic, and histopathological examinations were performed on all tissues. Results: ATP inhibited cisplatin-induced oxidative damage and pro-inflammatory cytokines levels in tongue tissue. In the CIS group, a significant number of distinct sulcus formations were found in the apex and corpus, as well as a few ulcer foci in the corpus, significant papilla loss, and bleeding. Meanwhile, in the ATP group, a similar appearance to healthy tissue was observed. Histopathologically, it was determined that in cisplatin-aggravated tongue tissue damage, filiform papillae decreased when ATP was administered, and the arrangement and structures of the epithelium, blood capillaries, muscle groups, and adipose cell groups were normal. Conclusions: Oral mucositis caused by cisplatin is alleviated by ATP. These findings may be useful for developing new therapeutic approaches to prevent or treat mucositis, a side effect so severe that can lead to treatment discontinuation.

Rutin (Vitamin P1) is an antioxidant and anti-inflammatory flavonoid. This study examined the effect of rutin on the potential of cisplatin to cause oxidative and proinflammatory damage in blood serum, ureter, bladder and urethra in rats. Animals were divided into four groups: (i) healthy (HG), (ii) 50 mg/kg of rutin + 5 mg/kg of cisplatin (C + R50), (iii) 100 mg/kg of rutin + 5 mg/kg of cisplatin (C + R100) and (iv) only cisplatin (CG). Rutin and distilled water were applied once a day for eight days. Cisplatin was injected intraperitoneally at a dose of 5 mg/kg for eight days, once every two days. Finally, animals were sacrificed by high -dose anesthesia after blood samples were taken. Ureter, bladder and urethra tissues were removed and malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), superoxide dismutase (SOD) interleukin beta (IL-1 beta) and tumor necrosis factor alpha (TNF-alpha) levels were measured. The results showed that the levels of MDA, MPO, IL-1 beta and TNF-alpha in the blood serum of the CG group increased significantly (p < 0.0001) and the tGSH and SOD levels decreased compared to the HG. Rutin administration reversed the effect as seen in C + R50 and C + R100 groups. However, there was no statistically significant difference in the levels of MDA, MPO, tGSH, SOD, IL-1 beta and TNF-alpha in ureter, bladder and urethra tissue (p > 0.05).This suggests that cisplatin produces oxidative stress in the blood serum but not in the ureter, bladder and urethra tissues. It was observed that rutin prevented the cisplatin-related oxidative and proinflammatory damage in the blood serum.