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    Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats
    (MASHHAD UNIV MED SCIENCES, 2025) Dokumacıoğlu, Eda; İskender, Hatice; Terim Kapakin, Kübra Asena; Bolat, İsmail; Mokhtare, Behzat; Ömür, Ali Doğan; Hayırlı, Armağan
    Objective(s): This experiment was carried out to investigate the protective effects of curcumin (CUR) on testicular damage induced by the valproic acid (VPA) administration. Materials and Methods: Male Wistar-Albino rats (n=28, 250-300 g) were randomly divided into four groups: Control (1 ml saline, oral), VPA (500 mg/kg, IP), CUR (200 mg/kg, oral), or VPA+CUR (500 mg/kg, VPA, IP plus 200 mg/kg CUR, oral). The treatments were applied for 14 days. Serum testosterone and testis [Janus kinases1 (JAK1), signal transducers and activators of transcription-3 interleukin-18 (IL-18), and nuclear factor (NF)-kappa B)] samples were collected for biochemical analyses. Semen samples were subjected to microscopy for spermatological parameters. Testis tissue was also analyzed for histopathological and immunohistochemical methods. Results: The VPA administration caused a 37% decrease in serum testosterone concentration and 5.32, 9.51, 2.44, and 3.68-fold increases in testicular tissue JAK1, STAT-3, IL-6, and MDA levels, respectively. There were also 50, 52, and 72% reductions in sperm motility, sperm viability, and the mean testicular biopsy score, respectively, accompanied by considerable degenerative changes and necrosis in seminiferous tubules in the VPA group. There is also an immune-positive reaction for IL-18 and NF-kappa B in only Leydig cells. Conclusion: The CUR treatment may be beneficial in restoring testicular damage through antiinflammatory and anti-oxidant potential.
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    Effect of betulinic acid administration on tlr-9/nf-κb /il-18 levels in experimental liver injury
    (TUBITAK Scientific & Technical Research Council Turkey, 2021) Dokumacıoğlu, Eda; İskender, Hatice; Terim Kapakin, Kübra Asena; Yenice, Güler; Mokthare, Behzat; Bolat, İsmail; Hayırlı, Armağan
    Background/aim: Acetaminophen (APAP), used in the composition of thousands of preparations, is the most commonly used analgesic and antipyretic drug. The present study aimed to investigate the potential protective effects of the betulinic acid (BA) treatment through an APAP-induced hepatotoxicity rat model, using inflammatory, biochemical, and histopathological parameters. Materials and methods: The study consisted of four groups: control group, APAP group, BA group, and APAP+BA group. Experimental studies continued for fifteen days. Serum samples were analysed for glucose, total cholesterol (TChol), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), aspartate amino transferase (AST), malondialdehyde (MDA), toll-like receptor-9 (TLR-9), nuclear factor kappa B (NF-kappa B), and interleukin-18 (IL-18). Results: TLR9, IL-18, NF-kappa B, and MDA levels increased significantly in liver injury groups. These increases considerably decreased by the BA treatment. All groups showed immunopositivity for 8-hydroxy-2 & rsquo;& ndash;deoxyguanosine (8-OHdG) and interleukin (IL-1 beta) in the hepatocytes, inflammatory cells, and epithelial cells of bile ducts. Conclusion: BA can be used as an effective agent in the prevention and treatment of acute liver diseases due to its inhibitory properties in multiple pathways and its potent antioxidant effects.
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    Effect of oleanolic acid administration on hepatic AMPK, SIRT-1, IL-6 and NF-κB levels in experimental diabetes
    (Springer Link, 2023) İskender, Hatice; Dokumacıoğlu, Eda; Terim Kapakin, Kübra Asena; Bolat, İsmail; Mokhtare, Behzat; Hayırlı, Armağan; Yenice, Güler
    Diabetes mellitus (DM) is an important public health problem all over the world, considering its complications and increasing prevalence. Oleanolic acid (OA) has anti-diabetic property via modulating glucose metabolism and acting as 5?–adenosine monophosphate (AMP)–activated protein kinase (AMPK) / Sirtuin–1 (SIRT–1) activator and Interleukin 6 (IL–6) / Nuclear factor kappa B (NF–?B) inhibitor. This research questioned if the OA treatment amliorates the hepatic inflammatory profile in the diabetic rats
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    Effects of oleanolic acid on inflammation and metabolism in diabetic rats
    (Taylor & Francis Inc, 2021) İskender, Hatice; Dokumacıoğlu, Eda; Terim Kapakın, Kübra Asena; Yenice, Güler; Mohtare, Behzat; Bolat, İsmail; Hayırlı, Armağan
    Diabetes mellitus (DM) is a chronic metabolic disease that threatens the health of the world population. We investigated the effects of oleanolic acid (OA) administration on inflammation status and metabolic profile in streptozotocin (STZ) induced diabetic rats. Four experimental groups were established: healthy rats not administered OA, healthy rats administered OA, diabetic rats not administered OA, diabetic rats administered OA. OA, 5 mg/kg, was administered by oral gavage for 21 days. Serum samples collected at the end of the experiment and analyzed for toll-like receptor-9, interleukin-18, nuclear factor kappa B, malondialdehyde MDA, glucose, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, calcium, phosphorus, magnesium and potassium. Pancreas tissue was examined for pathology. Induction of DM caused increased serum concentrations of inflammation and oxidative damage markers. DM also caused hyperglycemia-hyperlipidemia and decreased serum concentration of minerals. The islets of Langerhans were degenerated and necrotic. Administration of OA reversed the adverse effects of DM. OA treatment can ameliorate inflammation and oxidative damage due to DM by normalizing hyperglycemia and decreasing TLR-9, IL-18, NF-kappa B and MDA levels.
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    Protective effect of betulinic acid administration on kidney damage in acetaminophen-induced nephrotoxicity model
    (UNIV INDONESIA, 2023) Dokumacıoğlu, Eda; İskender, Hatice; Hayırlı, Armağan; Yenice, Güler; Terim Kapakin, Kübra Asena; Bolat, İsmail; Manavoğlu Kirman, Esra
    Background: Acetaminophen (APAP) is the most widely used analgesic drug worldwide, but it may induce renal toxicity. Betulinic acid (BA) ameliorates the oxidative stress and inflammatory response to renal damage. The present study aimed to investigate the potential protective effects of BA treatment through an experimental kidney damage rat model administered with APAP. Methods: Sprague-Dawley male rats were randomly divided into four groups: control, BA (25 mg/kg for 15 days), APAP (1 g/kg), and APAP + BA groups. BA was administered via oral gavage at a dose of 25 mg/kg for 15 days. APAP was dissolved in hot saline and administered on the last day to produce nephrotoxicity via a single oral gavage at a dose of 1 g/kg. Kidney tissue samples were analyzed for human cartilage glycoprotein 39 (YKL-40), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), superoxide dismutase (SOD), and malondialdehyde (MDA). Data were subjected to one-way analysis of variance and the Wilcoxon rank-sum test Results: Renal tissue YKL-40, KIM-1, IL-18, and MDA levels in the APAP group were significantly higher than those in the control group (p < 0.05). The BA treatment completely restored renal KIM-1, YKL-40, and MDA levels and partially restored renal IL-18 and SOD levels in the rats subjected to renal damage induction (p < 0.05). The intertubular regions of rats administered with APAP had degeneration, necrosis, and infiltration of inflammatory cells and were immunopositive for IL-1 beta and 8-hydroxy-2 & PRIME;-deoxyguanosine. Conclusions: BA can be used in the prevention and replacement treatment of nephrotoxicity due to its inhibitory properties in multiple pathways and powerful antioxidant effects.
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    Protective effects of curcumin against valproic acid induced brain kidney and liver damage in rats
    (Taylor and Francis Ltd., 2024) Terim Kapakin, Kübra Asena; Bolat, İsmail; İskender, Hatice; Dokumacioğlu, Eda; Manavoğlu Kirman, Esra; Bolat, Merve; Gül, Mevlana
    Valproic acid (VPA) is a broad-spectrum drug that is now widely used as an antiepileptic. Although VPA has positive therapeutic effects, it also causes various toxic effects in tissues. Curcumin, a natural antioxidant found in ginger, has antibacterial and antiinflammatory activity. In this study, the toxic effects of VPA on brain, kidney, and liver tissues and the protective activity of curcumin against these effects were investigated. In this study, male Wistar-Albino rats were used. Rats were divided into 4 groups control, VPA, CUR, and CUR + VPA. Rats were administered intraperitoneal VPA and CUR intragastrically. In the study, MDA, SOD, IL-6, and IL-18 levels were measured by the ELISA method in rats. It was observed that VPA triggered oxidative stress and inflammation in tissues, while CUR administration positively regulated these parameters. Studies also showed that VPA increased the expressions of TNF-? and NF-kB in tissues, but CUR administration downregulated these expressions The findings revealed that CUR protects by preventing the oxidative stress and inflammation caused by VPA in the tissues and may be an important agent in reducing the side effects of this drug used as an antiepileptic.