Hypothyroidism: morphological and metabolic changes in the testis of adult albino rat and the amelioration by alpha-lipoic acid
, 4, 54, 16
Abstract
Background: The objective of this study is to evaluate the influence of carbimazole- induced hypothyroidism on the testes of adult albino rats and the probable protective effect of alpha-lipoic acid (ALA). Materials and methods: The rats were divided into four groups; control group, ALA group, carbimazole, and carbimazole + ALA groups. Rats were exposed to ALA (60 mg/kg body weight) or carbimazole (1.35 mg/kg body weight), or both, administered via gavages for 30 days. Results: Morphometric analysis revealed a significant decrease in tubular diameter, germinal epithelium thickness, and interstitial space as compared to the controls. Also, rats exposed to carbimazole showed a significant decline in testicular weight, sperm motility, and count. Additionally, deterioration of the testicular architecture was observed. ALA supplementation resulted in a significant improvement in the tubular diameter and germinal epithelium thickness, but no significant improvement regarding interstitial space was observed. Another observation was the significant decline in serum testosterone and follicle-stimulating hormone (FSH) in the carbimazole group, indicating reduced steroidogenesis. A significant reduction in reduced glutathione content was detected in the testes of the carbimazole group compared with the controls, while malonaldehyde concentration significantly increased. Conversely, ALA supplementation ameliorated the toxicity induced by hypothyroidism as illustrated by enhanced reproductive organ weights, testosterone, luteinizing hormone, and FSH levels, testicular steroidogenesis, and oxidative stress parameters. Conclusions: Hypothyroidism altered testicular antioxidant balance and negatively affected spermatogenesis. On the other hand, ALA through its antioxidant properties alleviated testicular toxicity in carbimazole-exposed rats.
Keywords: alpha-lipoic acidcarbimazolehypothyroidismtestisrat
References
- Albus U. Guide for the Care and Use of Laboratory Animals (8th Ed). In Laboratory Animals. 2012.
- Asadi N, Bahmani M, Kheradmand A, et al. The impact of oxidative stress on testicular function and the role of antioxidants in improving it: a review. J Clin Diagn Res. 2017; 11(5): IE01–IE05.
- Bancroft JD, Gamble M. Theory and practice of histological techniques. Elsevier Health Sciences. 2008.
- Bell CA. Clinical guide to laboratory tests. Norbert W Tietz (3rd edn). Transfusion. 1995; 35(11): 972.
- Cronan JE, Zhao X, Jiang Y. Function, attachment and synthesis of lipoic acid in Escherichia coli. Adv Microb Physiol. 2005; 50: 103–146.
- Delitala AP, Capobianco G, Cherchi PL, et al. Thyroid function and thyroid disorders during pregnancy: a review and care pathway. Arch Gynecol Obstet. 2019; 299(2): 327–338.
- Divakaruni AS, Wiley SE, Rogers GW, et al. Thiazolidinediones are acute, specific inhibitors of the mitochondrial pyruvate carrier. Proc Natl Acad Sci U S A. 2013; 110(14): 5422–5427.
- El Hassani RA, Buffet C, Leboulleux S, et al. Oxidative stress in thyroid carcinomas: biological and clinical significance. Endocr Relat Cancer. 2019; 26(3): R131–R143.
- El-Maraghy SA, Nassar NN. Modulatory effects of lipoic acid and selenium against cadmium-induced biochemical alterations in testicular steroidogenesis. J Biochem Mol Toxicol. 2011; 25(1): 15–25.
- Gautam DK, Misro MM, Chaki SP, et al. H2O2 at physiological concentrations modulates Leydig cell function inducing oxidative stress and apoptosis. Apoptosis. 2006; 11(1): 39–46.
- Gawish AM. The protective role of alpha lipoic acid against pesticides induced testicular toxicity- histopathological and histochemical studies. J Aquaculture Res Development. 2010; 1(1): 101.
- Gosteli-Peter MA, Harder BA, Eppenberger HM, et al. Triiodothyronine induces over-expression of alpha-smooth muscle actin, restricts myofibrillar expansion and is permissive for the action of basic fibroblast growth factor and insulin-like growth factor I in adult rat cardiomyocytes. J Clin Invest. 1996; 98(8): 1737–1744.
- Ha AeW, Kim WK. The effect of fucoxanthin rich power on the lipid metabolism in rats with a high fat diet. Nutr Res Pract. 2013; 7(4): 287–293.
- Hernandez A, Martinez ME. Thyroid hormone action in the developing testis: intergenerational epigenetics. J Endocrinol. 2020; 244(3): R33–R46.
- Hofstee P, McKeating DR, Bartho LA, et al. Maternal selenium deficiency in mice alters offspring glucose metabolism and thyroid status in a sexually dimorphic manner. Nutrients. 2020; 12(1): 267.
- Holmquist L, Stuchbury G, Berbaum K, et al. Lipoic acid as a novel treatment for Alzheimer's disease and related dementias. Pharmacol Ther. 2007; 113(1): 154–164.
- Horibe A, Eid N, Ito Y, et al. Upregulated autophagy in sertoli cells of ethanol-treated rats is associated with induction of inducible nitric oxide synthase (inos), androgen receptor suppression and germ cell apoptosis. Int J Mol Sci. 2017; 18(5).
- Horibe A, Eid N, Ito Y, et al. Ethanol-Induced autophagy in sertoli cells is specifically marked at androgen-dependent stages of the spermatogenic cycle: potential mechanisms and implications. Int J Mol Sci. 2019; 20(1).
- Jalilvand N, Hosseini M, Beheshti F, et al. Protective effect of PPARγ agonist pioglitazone, on testicular tissue and sperm parameters in hypothyroid rats. Toxin Reviews. 2019; 24: 1–10.
- Kamel A, Hamouli-Said Z. Neonatal exposure to T3 disrupts male reproductive functions by altering redox homeostasis in immature testis of rats. Andrologia. 2018; 50(9): e13082.
- Karafakioğlu YS. Effects of α lipoic acid on noise induced oxidative stress in rats. Saudi J Biol Sci. 2019; 26(5): 989–994.
- Kopecky M, Semecky V, Nachtigal P. Vimentin expression during altered spermatogenesis in rats. Acta Histochem. 2005; 107(4): 279–289.
- Krassas GE, Markou KB. The impact of thyroid diseases starting from birth on reproductive function. Hormones (Athens). 2019; 18(4): 365–381.
- Krysiak R, Szkróbka W, Okopień B. The impact of testosterone on metformin action on hypothalamic-pituitary-thyroid axis activity in men: a pilot study. J Clin Pharmacol. 2020; 60(2): 164–171.
- Krytskyy T, Pasyechko N. Correction of androgen deficiency in men with hypothyroidism. Georgian Med News. 2019(286): 77–82.
- La Vignera S, Vita R, Condorelli RA, et al. Impact of thyroid disease on testicular function. Endocrine. 2017; 58(3): 397–407.
- La Vignera S, Vita R. Thyroid dysfunction and semen quality. Int J Immunopathol Pharmacol. 2018; 32: 2058738418775241.
- Naseem Z, Iqbal MA, Ahmad S, et al. Inflammatory markers as prognosticators of cardiovascular dysfunction in hypothyroid patients. J Biol Regul Homeost Agents. 2019; 33(6): 1891–1895.
- O'Hara L, Smith LB. Androgen receptor roles in spermatogenesis and infertility. Best Pract Res Clin Endocrinol Metab. 2015; 29(4): 595–605.
- Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979; 95(2): 351–358.
- Panait N, Michel F, D'Ercole C, et al. Esophageal atresia, small omphalocele and ileal prolapse through a patent omphalomesenteric duct: a methimazole embryopathy? [Corrected]. J Pediatr Surg. 2013; 48(6): E9–11.
- Prathima P, Venkaiah K, Pavani R, et al. α-lipoic acid inhibits oxidative stress in testis and attenuates testicular toxicity in rats exposed to carbimazole during embryonic period. Toxicol Rep. 2017; 4: 373–381.
- Rebar RW, Morandini IC, Petze JE, et al. Hormonal basis of reproductive defects in athymic mice: reduced gonadotropins and testosterone in males. Biol Reprod. 1982; 27(5): 1267–1276.
- Romano RM, Bargi-Souza P, Brunetto EL, et al. Hypothyroidism in adult male rats alters posttranscriptional mechanisms of luteinizing hormone biosynthesis. Thyroid. 2013; 23(4): 497–505.
- Sakr SR, ELnaby SH, Okdah Y, et al. Impact of ginger aqueous extract on carbimazole induced testicular degenerative alterations and oxidative stress in albino rats. J Coastal Life Med. 2017; 5(4): 167–173.
- Saha I, Chakraborty SB, Chatterjee A, et al. Arecoline inhibits pineal-testis function in experimentally induced hypothyroid rats. Arch Physiol Biochem. 2020; 126(1): 7–16.
- Schlorff EC, Husain K, Somani SM. Dose and time dependent effects of ethanol on antioxidant system in rat testes. Alcohol. 1999; 18(2-3): 203–214.
- Sedlak J, Lindsay RH. Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman's reagent. Anal Biochem. 1968; 25(1): 192–205.
- Shalaby AM, Ibrahim MA, Aboregela AM. Effect of aspartame on the placenta of adult albino rat. A histological and immunohistochemical study. Ann Anat. 2019; 224: 133–141.
- Sharpe RM. Environmental/lifestyle effects on spermatogenesis. Philos Trans R Soc Lond B Biol Sci. 2010; 365(1546): 1697–1712.
- Tutelyan VA, Makhova AA, Pogozheva AV, et al. [Lipoic acid: physiological role and prospects for clinical application]. Vopr Pitan. 2019; 88(4): 6–11.
- Xiang W, Wang Li, Cheng S, et al. Protective effects of α-Lipoic acid on vascular oxidative stress in rats with hyperuricemia. Curr Med Sci. 2019; 39(6): 920–928.
- Yousofvand N, Kazemi M, Mohammadizadeh E. Effect of induced hypothyroidism by propiltiouracil (PTU) on serum levels of testosterone, luteinizing hormone, follicle stimulating hormone in adult rat. Scientific J Ilam University Med Sci. 2013; 21(6): 1–8.
- Zamoner A, Barreto KP, Filho DW, et al. Propylthiouracil-induced congenital hypothyroidism upregulates vimentin phosphorylation and depletes antioxidant defenses in immature rat testis. J Mol Endocrinol. 2008; 40(3): 125–135.
