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Dokumacioglu, Eda, Iskender, Hatice, Bolat, ismail, Kapakin, Kubra, Mokhtare, Behzat, Omur, Ali, Hayirli, Armagan. (1403). Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats. , 28(2), 230-236. doi: 10.22038/ijbms.2024.76948.16659
Eda Dokumacioglu; Hatice Iskender; ismail Bolat; Kubra Asena Terim Kapakin; Behzat Mokhtare; Ali Dogan Omur; Armagan Hayirli. "Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats". , 28, 2, 1403, 230-236. doi: 10.22038/ijbms.2024.76948.16659
Dokumacioglu, Eda, Iskender, Hatice, Bolat, ismail, Kapakin, Kubra, Mokhtare, Behzat, Omur, Ali, Hayirli, Armagan. (1403). 'Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats', , 28(2), pp. 230-236. doi: 10.22038/ijbms.2024.76948.16659
Dokumacioglu, Eda, Iskender, Hatice, Bolat, ismail, Kapakin, Kubra, Mokhtare, Behzat, Omur, Ali, Hayirli, Armagan. Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats. , 1403; 28(2): 230-236. doi: 10.22038/ijbms.2024.76948.16659

Curcumin exerts protective effects against valproic acid-induced testicular damage through modulating the JAK1/STAT–3/IL–6 signaling pathway in rats

Iranian Journal of Basic Medical Sciences
مقاله 11، دوره 28، شماره 2، اردیبهشت 2025، صفحه 230-236    اصل مقاله (380.07 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2024.76948.16659
نویسندگان
Eda Dokumacioglu* 1؛ Hatice Iskender1؛ ismail Bolat2؛ Kubra Asena Terim Kapakin2؛ Behzat Mokhtare3؛ Ali Dogan Omur4؛ Armagan Hayirli5
1Eda Dokumacioglu, Department of Nutrition and Dietetics, Faculty of Health Sciences, Artvin Coruh University, Artvin 08000, Turkey
2Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, Turkey
3Department of Pathology, Faculty of Veterinary Medicine, Dicle University, Diyarbakır, 21000, Turkey
4Ali Dogan Omur, Department of Reproduction and Artificial Insemination, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, Turkey
5Department of Animal Nutrition and Nutritional Disorders, Faculty of Veterinary Medicine, Ataturk University, Erzurum 25240, Turkey
چکیده
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 (STAT–3), interleukin–6 (IL–6), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF–α), interleukin–18 (IL–18), and nuclear factor (NF)–κB)] 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–κB in only Leydig cells. 
Conclusion: The CUR treatment may be beneficial in restoring testicular damage through antiinflammatory and anti-oxidant potential.
کلیدواژه‌ها
Curcumin؛ Interleukin–6؛ Janus kinases؛ Testicular damage؛ Valproic acid
مراجع
1. Zhu MM, Li HL, Shi LH, Chen XP, Luo J, Zhang ZL. The pharmacogenomics of valproic acid. J Hum Genet 2017; 62: 1009–1014. 
2. Goldberg–Stern H, Yaacobi E, Phillip M, de Vries L. Endocrine effects of valproic acid therapy in girls with epilepsy: A prospective study. Eur J Paediatr Neurol 2014; 18: 759–765. 
3. Romoli M, Mazzocchetti P, D’Alonzo R, Siliquini S, Rinaldi VE, Verrotti A, Calabresi P, Costa C. Valproic acid and epilepsy: From molecular mechanisms to clinical evidences. Curr Neuropharmacol 2019; 17: 926–946. 
4. Nishimura T, Sakai M, Yonezawa H. Effects of valproic acid on fertility and reproductive organs in male rats. J Toxicol Sci 2000; 25: 85–93. 
5. Iamsaard S, Sukhorum W, Arun S, Phunchago N, Uabundit N, Boonruangsri P, Namking M. Valproic acid induces histologic changes and decreases androgen receptor levels of testis and epididymis in rats. Int J Reprod Biomed 2017; 15: 217–224. 
6. Kowshik J, Baba AB, Giri H, Deepak–Reddy G, Dixit M, Nagini S. Astaxanthin inhibits JAK/STAT–3 signaling to abrogate cell proliferation, invasion and angiogenesis in a hamster model of oral cancer. PLoS One 2014; 9: e109114. 
7. Baba AB, Nivetha R, Chattopadhyay I, Nagini S. Blueberry and malvidin inhibit cell cycle progression and induce mitochondrial–mediated apoptosis by abrogating the JAK/STAT–3 signalling pathway. Food Chem Toxicol 2017;109: 534–543. 
8. Chang X, Hu LF, Ma XJ, Yin J, Liu XY, Li JB. Influence of roflumilast on sepsis mice through the JAK/STAT signaling pathway. Eur Rev Med Pharmacol Sci 2019; 23: 1335–1341. 
9. Parameswaran N, Patial S. Tumor necrosis factor-α signaling in macrophages. Crit Rev Eukaryot Gene Expr 2010; 20: 87–103. 
10. Sharifi-Rad J, Rayess YE, Rizk AA, Sadaka C, Zgheib R, Zam W, et al. Turmeric and its major compound curcumin on health: Bioactive effects and safety profiles for food, pharmaceutical, biotechnological and medicinal applications. Front Pharmacol 2020; 11: 01021. 
11. Yalçın AS, Yılmaz AM, Altundağ EM, Koçtürk S. Anti-cancer effects of curcumin, quercetin and tea catechins. Marmara Pharmaceutical J 2017; 21: 19–29. 
12. Park J, Conteas CN. Anti–carcinogenic properties of curcumin on colorectal cancer. World J Gastrointest Oncol 2010; 2: 169–176. 
13. Ahmadabady S, Beheshti F, Shahidpour F, Khordad E, Hosseinid MA. Protective effect of curcumin on cardiovascular oxidative stress indicators in systemic inflammation induced by lipopolysaccharide in rats. Biochem Biophys Rep 2021; 25: 100908. 
14. Hewlings SJ, Kalman DS. Curcumin: A review of its effects on human health. Foods 2017; 6: 92-102. 
15. Sarıyer ET, Aksu BM. Curcumin and gastrointestinal system diseases. J Biotechnol  Strategic Health Res 2020; 4: 194–205. 
16. Iqbal U, Anwar H, Quadri AA. Use of curcumin in achieving clinical and endoscopic remission in ulcerative colitis: A systematic review and meta-analysis. Am J Med Sci 2018;  356: 350–356. 
17. Alok A, Singh ID, Singh S, Kishore M, Jha PC. Curcumin – pharmacological actions and its role in oral submucous fibrosis: A review. J Clin Diagn Res. 2015 Oct; 9: ZE01–ZE03.
18. Joe B, Vijaykumar M, Lokesh BR. Biological properties of curcumin–cellular and molecular mechanisms of action. Crit Rev Food Sci Nut. 2004; 44: 97–111.
19. Aksu EH, Kandemir FM, Yıldırım S, Küçükler S, Dörtbudak MB, Çağlayan C, Benzer F. Palliative effect of curcumin on doxorubicin–induced testicular damage in male rats. Biochem Mol Toxicol 2019; 33: e22384. 
20. Esterbauer X H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4–hidroxynonenal. Methods Enzymol 1990;186: 407–421. 
21. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein‑dye binding. Anal Biochem 1976; 72: 248‑54.
22. Ömür AD, Apaydın Yıldırım B, Kandemir MF, Akman O, Aktaş Şenocak E, Aksu EH. Can taraxacum officinale (dandelion) extract be an alternative of paracetamol in inflammatory and painful cases? An evaluation with regard to biochemical and reproductive parameters. Kafkas Univ Vet Fak Derg 2017; 23: 47-54. 
23. Turk G, Atessahin A, Sonmez M, Ceribasi AO, Yuce A. Improvement of cisplatin–induced injuries to sperm quality, the oxidant–antioxidant system, and the histologic structure of the rat testis by ellagic acid. Fertil Steril 2008; 89:1474–1481. 
24.Aksu EH, Akman O, Ozkaraca M, Omur AD, Ucar O. Effect of maclura pomifera extract against cisplatin–induced damage in reproductive system of male rats. Kafkas Univ Vet Fak Derg 2015; 21:397–403. 
25. Aksu EH, Özkaraca M, Kandemir FM, Ömür AD, Eldutar E, Küçükler S, Çomaklı S. Mitigation of paracetamol-induced reproductive damage by chrysin in male rats via reducing oxidative stress. Andrologia 2016; 48: 1145-1154. 
26. Dokumacioglu E, Iskender H, Yenice G, Kapakin KAT, Sevim C, Hayirli A, et al. Effects of astaxanthin on biochemical and histopathological parameters related to oxidative stress on testes of rats on high fructose regime. Andrologia 2018;50: e13042. 
27. Apaydin–Yildirim B, Kordali S, Terim–Kapakin KA, Yildirim F, Aktas–Senocak E, Altun S. Effect of Helichrysum plicatum DC. subsp. plicatum ethanol extract on gentamicin–induced nephrotoxicity in rats. J Zhejiang Univ Sci B 2017;18: 501–511. 
28. Johnsen SG. Testicular biopsy score count a method for registration of spermatogenesis in human testes: Normal values and results in 335 hypogonadal males. Hormones 1970;1:2–25. 
29. Terim–Kapakin K, Imik H, Gumus R, Kapakin S, Sağlam Y. Effect of Vit E on secretion of HSP–70 in testes of broilers exposed to heat stress. Kafkas Univ Vet Fak Derg 2013; 19:305-310. 
30. Mirza R, Sharma B. Beneficial effects of pioglitazone, a selective peroxisome proliferator–activated receptor–γ agonist in prenatal valproic acid–induced behavioral and biochemical autistic like features in Wistar rats. Int J Dev Neurosci 2019; 76:6–16. 
31. Cansu A, Ekinci Ö, Serdaroglu A, Gürgen S G, Ekinci Ö, Erdogan D, Coskun ZK, Tunc L. Effects of chronic treatment with valproate and oxcarbazepine on testicular development in rats. Seizure 2011; 20: 203–207. 
32.Ahmed, N, Aljuhani N, Al–Hujaili HS, Al–Hujaili MA, Elkablawy MA, Noah MM, Abo-Haded H, El-Agamy DS. Agmatine protects against sodium valproate induced hepatic injury in mice via modulation of nuclear factor–κB/inducible nitric oxide synthetase pathway. J Biochem Mol Toxicol 2018; 32: e22227. 
33.Gai Z, Krajnc E, Samodelov SL, Visentin M, Kullak–Ublick GA. Obeticholic acid ameliorates valproic acid–induces hepatic steatosis and oxidative stress. Mol Pharmacol 2020; 97: 314–323. 
34. Turkyilmaz IB, Altas N, Arisan I, Yanardag R. Effect of vitamin B6 on brain damage in valproic acid induced toxicity. J Biochem Mol Toxicol 2021; 35: e22855. 
35. Bairy L, Paul V, Rao Y. Reproductive toxicity of sodium valproate in male rats. Indian J Pharmacol 2010; 42: 90–94. 
36. Dabrowska Z, Dąbrowska E, Onopiuk B, Onopiuk P, Orywal K, Mroczko B, Pietruska M. The protective impact of black chokeberry fruit extract (Aronia melanocarpa L.) on the oxidoreductive system of the parotid gland of rats exposed to cadmium. Oxid Med Cell Longev 2019; 2019: 1–11. 
37. Çelik Ç, Bayrak BB, Hacıhasanoğlu Çakmak N, Yanardağ R. Protective effect of edaravone on rat testis after valproic acid treatment. J Res Pharm 2022; 26: 52–62. 
38. Sharma S, Sharma V, Pracheta SSH. Therapeutic potential of hydromethanolic root extract of Withania somnifera on neurological parameters in Swiss Albino mice subjected to lead nitrate. Int J Current Pharm Res 2011; 3:52–56. 
39. Ourique GM, Saccol EM, Pês TS, Glanzner WG, Schiefelbein SH, Woehl VM, Baldisserotto B, Pavanato MA, Gonçalves PB, Barreto KP. Protective effect of vitamin E on sperm motility and oxidative stress in valproic acid-treated rats. Food Chem Toxicol 2016; 95: 159–167. 
40. Sukhorum W, Iamsaard S. Changes in testicular function proteins and sperm acrosome status in rats treated with valproic acid. Reprod Fertil Dev 2017; 29: 1585–1592. 
41. Turner TT, Lysiak JJ. Oxidative stress: A common factor in testicular dysfunction. J Androl 2008; 29: 488–498. 
42. Roste L S, Tauboll E, Berner A, Berg KA, Aleksandersen M, Gjerstad L. Morphological changes in the testis after long–term valproate treatment in male Wistar rats. Seizure 2001; 10: 559–565. 
43. Zhang L, Zuo QS, Li D, Lian C, Ahmed EK, Tang BB, Song SJ, Zhang YN, Li BC. Study on the role of JAK/STAT signaling pathway during chicken spermatogonial stem cells generation based on RNA–Seq.  J Integr Agric 2015; 14: 939–948. 
44. Li J, Zhang L, Li B. Correlative study on the JAK–STAT/PSMβ3 signal transduction pathway in asthenozoospermia. Exp Ther Med 2016;13: 127–130. 
45. Alves–Silva T, Freitas GA, Húngaro TGR, Arruda AC, Oyama LM, Avellar MCW, Araujo RC. Interleukin–6 deficiency modulates testicular function by increasing the expression of suppressor of cytokine signaling 3 (SOCS3) in mice. Sci Rep 2021;11: 11456. 
46. Savran M, Ascı H, Armagan I, Erzurumlu Y, Azırak S, Kaya–Ozer M, Bilgic S, Korkmaz DT. Thymoquinone could be protective against valproic acid-induced testicular toxicity by antioxidant and antiinflammatory mechanisms. Andrologia 2020; 52: e13623. 
47. Panahi Y, Hosseini MS, Khalili N, Naimi E, Simental–Mendia LE, Majeed M, Sahebkar A. Effects of curcumin on serum cytokine concentrations in subjects with metabolic syndrome: A post–hoc analysis of a randomized controlled trial. Biomed Pharmacother 2016; 82: 578–582.

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