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    Dose-Dependent Pulmonotoxic Effects of Favipiravir in Rats Biochemical and Histopathological Evaluation
    (Asian Network Scientific Information-Ansinet, 2025) Suleyman, Zeynep; Altuner, Durdu; Suleyman, Halis; Coban, Taha Abdulkadir; Ozkaraca, Mustafa
    Background and Objective: Favipiravir is associated with more serious side effects at higher doses. This experimental study proposed to investigate the effect of favipiravir on dose-dependent lung toxicity in rats biochemically and histopathologically. Materials and Methods: The rats were divided into four groups as healthy (HG), 100 mg/kg favipiravir (FAV-100), 200 mg/kg favipiravir (FAV-200) and 400 mg/kg favipiravir (FAV-400). Favipiravir 100, 200 and 400 mg/kg doses were administered by oral gavage to the other groups except HG. To the HG group, only distilled water (0.5 mL) was applied in the same way. This procedure was repeated twice a day for a week. Then, the rats were euthanised with high-dose anaesthesia and lung tissues were removed. Oxidative stress parameters such as malondialdehyde (MDA), Total Glutathione (tGSH), superoxide dismutase (SOD), total oxidant status (TOS) and total antioxidant status (TAS) were examined. After the one-way ANOVA, the Tukey's post hoc test was performed. Results: Favipiravir dose-dependently increased MDA and TOS also decreased tGSH, SOD and TAS in rat lung tissue. As favipiravir was given in increasing doses, it was easier to observe the changes between the different groups. This was also supported by the histopathological data. Histopathologically, interstitial pneumonia and lymphoid hyperplasia were mild in the 100 mg/kg favipiravir group, severe at high doses. Conclusion: As the dose of favipiravir increased, oxidant levels increased and antioxidant levels decreased in the lung tissue. In line with these results, it was observed that favipiravir caused a dose-dependent pulmonotoxic effect in rats.
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    Effect of taxifolin on acrylamide-induced oxidative and proinflammatory lung injury in rats: Biochemical and histopathological studies
    (Pharmacotherapy Group, 2022) Demir, Omer Faruk; Elma, Bekir; Suleyman, Bahadir; Ozkaraca, Mustafa; Mammadov, Renad; Suleyman, Halis; Coban, Taha Abdulkadir
    Purpose: To examine the probable beneficial effects of taxifolin against acrylamide damage in lung tissue. Methods: 18 male albino Wistar rats were divided into healthy (HG), acrylamide (AG) and taxifolin + acrylamide (TAG) groups. Once a day for 30 days, acrylamide was orally administered to the AG group (50 mg/kg), while ACL (50 mg/kg) and TAX (20 mg/kg) were orally administered to TAG group. Protein concentration, malondialdehyde (MDA), and total glutathione (tGSH) levels as well as oxidant and antioxidant molecules concentrations of the rat lung tissues were measured. In addition, degree of mononuclear (MN) cell infiltration and bronchial-associated lymphoid tissue (BALT) hyperplasia was evaluated by the degree of hyperplasia (absent, mild, moderate, severe). The histopathological and biochemical data the groups were compared. Results: When compared in terms of MDA levels, it was found that the AG group had high MDA levels, and the TAG group had low MDA levels. (p < 0.001). TAG group was found to have a higher tGSH level than the AG group (p < 0.001). Compared to the AG group, lower TOS and higher TAS levels were obtained in the TAG group (p < 0.001). In addition, when TOS levels of TAG and HG groups were compared, the TOS levels between the two groups were statistically insignificant (p = 0.213). It has been observed that TAX administration prevents the increase in NF-KB level. When the NF-KB levels of the AG and TAG groups were compared with each other, there was a statistically significant difference (p = 0.001). In the AG group, severe MN cell hyperplasia and BALT hyperplasia were observed histopathologically. It was determined that these findings were alleviated in the TAG group. A histopathologically significant difference was found between AG and TAG groups (p < 0.05). Conclusion: Taxifolin has beneficial effects against lung injury caused by acrylamide, a health damaging environmental factor. Regular use of taxifolin can be recommended, especially in people who are known to have intense contact with acrylamide. There is a need for research studies on this subject.
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    The effect of taxifolin on oxidative ovarian damage and reproductive dysfunctions induced by antipsychotic drugs in female rats
    (Wiley, 2021) Ince, Sefa; Ozer, Mehmet; Kadioglu, Berrin Goktug; Kuzucu, Mehmet; Ozkaraca, Mustafa; Gezer, Arzu; Suleyman, Halis
    Aim Typical antipsychotics (TAPs) are commonly used to treat schizophrenia and bipolar disorder. However, extrapyramidal disorders, hyperprolactinemia, and reproductive dysfunctions have been observed in women during the use of TAPs. For this reason, less toxic and prolactin-sparing atypical antipsychotic (AAP) drugs such as clozapine (CLN) have been developed. The aim of this study is to investigate the effect of taxifolin on possible ovarian and reproductive toxicity associated with CLN and haloperidol (HPL) in female Wistar albino rats. Methods The rats were grouped as healthy control group (HCG), CLN, HPL, taxifolin + clozapine (TCL), and taxifolin + haloperidol (THL). Drugs were administered to the groups for 28 days. At the end of that time, ovarian tissues of six rats from each group were taken for histopathological and biochemical analyses. Remaining six rats in groups were examined for evaluation of reproductive dysfunctions. Results Severe degeneration and vacuolization were observed in the primary, secondary, and primordial follicles of the ovarian tissues of CLN- and HPL-treated groups, of which malondialdehyde (MDA) level was high and total glutathione (tGSH) level was low. In the taxifolin-treated groups, taxifolin significantly prevented the increase of MDA level and decrease of tGSH level, and the severity of histopathological damage was found to be lower. In addition, it was found that taxifolin significantly prevented infertility and delay in pregnancy associated with CLN and HPL. Conclusions The results of this experiment suggest that taxifolin can be beneficial in treating oxidative ovarian damage, infertility, and reproductive dysfunctions induced by CLN and HPL.