Effects of testosterone replacement on lipid profile, hepatotoxicity, oxidative stress, and cognitive performance in castrated wistar rats

Published: November 15, 2023
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Objective: Androgen deficiency is associated with multiple biochemical and behavioral disorders. This study investigated the effects of testosterone replacement and Spirulina Platensis association on testosterone deficiency-induced metabolic disorders and memory impairment. Methods: Adult male rats were randomly and equally divided into four groups and received the following treatments for 20 consecutive days. Control group: non-castrated rats received distilled water. Castrated group received distilled water. Testosterone treated group: castrated rats received 0.20 mg of testosterone dissolved in corn oil by subcutaneous injection (i.p.). Spirulina co-treated group: castrated rats received 0.20 mg of testosterone (i.p.) dissolved in corn oil followed by 1000 mg/kg of Spirulina per os. Results: Data showed that castration induced an increase in plasma ALT, AST, alkaline phosphatase (PAL), cholesterol, and triglycerides level. Castrated rats showed a great elevation in SOD and CAT activities and MDA and H2O2 levels in the prostate, seminal vesicles, and brain. Testosterone deficiency was also associated with alteration of the spatial memory and exploratory behaviour. Testosterone replacement either alone or with Spirulina combination efficiently improved most of these biochemical parameters and ameliorated cognitive abilities in castrated rats. Conclusions: Testosterone replacement either alone or in combination with Spirulina improved castration-induced metabolic, oxidative, and cognitive alterations.

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Swerdloff RS, Wang C, Hines M, Gorski M. Effect of androgens on brain and other organs during development and aging, Psychoneuroendocrinology. 1992; 17:375. DOI: https://doi.org/10.1016/0306-4530(92)90042-6
Thirumalai A, Anawalt BD. Epidemiology of male hypogonadism. Endocrinol Met Clin. 2022; 5:1. DOI: https://doi.org/10.1016/j.ecl.2021.11.016
Marcelli M, Mediwala SN. Male hypogonadism: a review. J Investig Med. 2020; 68: 335. DOI: https://doi.org/10.1136/jim-2019-001233
Thilers P, Mac Donald S, Herlitz A. The association between endogenous free testosterone and cognitive performance: A population-based study in 35 to 90 year-old men and women. Psychoneuroendocrinology 2006; 31:565. DOI: https://doi.org/10.1016/j.psyneuen.2005.12.005
Dong X, Jiang H, Li S, Zhang D. Low Serum Testosterone Concentrations Are Associated with Poor Cognitive Performance in Older Men but Not Women. Frontiers Aging Neuroscience. 2021; 13:712237. DOI: https://doi.org/10.3389/fnagi.2021.712237
Jacome LF, Barateli K, Buitrago D, et al. Gonadal Hormones Rapidly Enhance Spatial Memory and Increase Hippocampal Spine Density in Male Rats. Endocrinology. 2016; 157:1357. DOI: https://doi.org/10.1210/en.2015-1959
Kritzer MF, McLaughlin PJ, Smirlis T, Robinson JK. Gonadectomy Impairs T-Maze Acquisition in Adult Male Rats. Horm Behav. 2001; 39: 167. DOI: https://doi.org/10.1006/hbeh.2001.1645
Mathiasen JR, diCamillo A. Novel object recognition in the rat: a facile assay for cognitive function. Current protocols in pharmacology. 2010; Chapter 5. DOI: https://doi.org/10.1002/0471141755.ph0559s49
Spritzer MD, Daviau ED, Coneeny MK, et al. Effects of testosterone on spatial learning and memory in adult male rats. Horm Behav. 2011; 59:484. DOI: https://doi.org/10.1016/j.yhbeh.2011.01.009
Hermoso DAM, Bizerra PFV, Constantin RP, et al. Association between metabolic syndrome, hepatic steatosis, and testosterone deficiency: evidences from studies with men and rodents. Aging Male. 2020; 23:1296. DOI: https://doi.org/10.1080/13685538.2020.1764927
Wagner BA, Braddick VC, Batson CG, et al. Effects of testosterone dose on spatial memory among castrated adult male rats. Psychoneuroendocrinology. 2018; 89:120. DOI: https://doi.org/10.1016/j.psyneuen.2017.12.025
Rovira-Llopis S, Bañuls C, de Marañon AM, et al. Low testosterone levels are related to oxidative stress, mitochondrial dysfunction and altered subclinical atherosclerotic markers in type 2 diabetic male patients. Free Radic Biol Med. 2017; 108:155. DOI: https://doi.org/10.1016/j.freeradbiomed.2017.03.029
Al-Zoubi RM, Yassin AA, Alwani M et al. A systematic review on the latest developments in testosterone therapy: Innovations, advances, and paradigm shifts. Arab J Urol. 2021; 19:370. DOI: https://doi.org/10.1080/2090598X.2021.1959260
Michaud JE, Billups KL, Partin AW. Testosterone and prostate cancer: an evidence-based review of pathogenesis and oncologic risk. Ther Adv Urol. 2015; 7:378. DOI: https://doi.org/10.1177/1756287215597633
Grech A, Breck J, Heidelbaugh J. Adverse effects of testosterone replacement therapy: an update on the evidence and controversy. Ther Adv Drug Saf. 2014; 5:190. DOI: https://doi.org/10.1177/2042098614548680
Banihani SA. Testosterone in Males as Enhanced by Onion (Allium Cepa L.). Biomolecules. 2019; 9:75. DOI: https://doi.org/10.3390/biom9020075
Banihani SA. Ginger and Testosterone. Biomolecules. 2018; 8:119. DOI: https://doi.org/10.3390/biom8040119
Zahran WE, Emam MA. Renoprotective effect of spirulina platensis extract against nicotin-induced oxidative stress mediated inflammation in rats. Phytomedicine. 2018; 49:106. DOI: https://doi.org/10.1016/j.phymed.2018.06.042
El Far OA, Billa N, Lim HR et al. Advances in delivery methods of Arthrospira platensis (Spirulina) for enhanced therapeutic oatcomes. Bioengineered. 2022; 13:14681. DOI: https://doi.org/10.1080/21655979.2022.2100863
Germoush MO, Fonda MMA, Kamal M, Abdel-Daim MM. Spirulina platensis protects against microcystin-LR-induced toxicity in rats. Environ. Sci Pollut Res Int. 2022; 29:11320. DOI: https://doi.org/10.1007/s11356-021-16481-y
Gutiérrez-Salmeán G, Fabila-Castillo L, Chamorro-Cevallos G. Nutritional and toxicological aspects of spirulina (arthrospira). Nutr Hosp. 2015; 32:34.
Barkallah M, Ben Slima A, Elleuch F, et al. Protective Role of Spirulina platensis against Bifenthrin-Induced Reprotoxicity in Adult Male Mice by Reversing Expression of Altered Histological, Biochemical, and Molecular Markers Including MicroRNAs. Biomolecules. 2020; 10:753. DOI: https://doi.org/10.3390/biom10050753
Abd El-Hakim YM, Mohamed WA, El-Metwally AE. Spirulina platensis attenuates furan reprotoxicity by regulating oxidative stress, inflammation, and apoptosis in testis of rats. Ecotoxicol Environ Saf. 2018; 161:25. DOI: https://doi.org/10.1016/j.ecoenv.2018.05.073
Hwang JH, Lee IT, Jeng KC, et al. Spirulina prevents memory dysfunction, reduces oxidative stress damage and augments antioxidant activity in senescence-accelerated mice. J Nutr Sci Vitaminol. 2011; 57:186. DOI: https://doi.org/10.3177/jnsv.57.186
Park BK, Kim CW, Kwon JE, et al. Effects of Lespedeza Cuneata aqueous extract on testosterone-induced prostatic hyperplasia. Pharm Biol. 2019; 57:90. DOI: https://doi.org/10.1080/13880209.2018.1564929
Jaeger ECB, Miller LE, Goins EC, et al. Testosterone replacement causes dose-dependent improvements in spatial memory among aged male rats. Psychoneuroendocrinology. 2020; 113:104550. DOI: https://doi.org/10.1016/j.psyneuen.2019.104550
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem. 1976; 72:248. DOI: https://doi.org/10.1016/0003-2697(76)90527-3
Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972; 247:3170. DOI: https://doi.org/10.1016/S0021-9258(19)45228-9
Aebi H. Catalase in vitro. Methods Enzymol. 1984; 104:121. DOI: https://doi.org/10.1016/S0076-6879(84)05016-3
Draper HH, Hadley M. Malondialdehyde determination as index of lipid Peroxidation. Methods Enzymol 1990; 189:421. DOI: https://doi.org/10.1016/0076-6879(90)86135-I
Jabri MA, Rtibi K, Sebai H. Chamomile decoction mitigates high fat diet-induced anxiety-like behavior, neuroinflammation and cerebral ROS overload. Nutritional Neuroscience. 2022; 25:1350. DOI: https://doi.org/10.1080/1028415X.2020.1859727
Denninger JK, Smith BM, Kirby ED. Novel object recognition and object location behavioral testing in mice on a budget. J Vis Exp. 2018; 141:58593. DOI: https://doi.org/10.3791/58593-v
Lueptow LM. Novel object recognition test for the investigation of learning and memory in mice. J Vis Exp. 2017; 126:e55718. DOI: https://doi.org/10.3791/55718-v
Antunes M, Biala G. The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process. 2012; 13:93. DOI: https://doi.org/10.1007/s10339-011-0430-z
Errazuriz I, Dube S, Basu A, Basu RM. Effects of testosterone on glucose and lipid metabolism. Cardivas Edocrinol. 2015; 4:95. DOI: https://doi.org/10.1097/XCE.0000000000000061
Birzneice V. Hepatic actions of androgens in the regulation of metabolism. Curr Opi Endocrinol Diabetes Obes. 2018; 25:201. DOI: https://doi.org/10.1097/MED.0000000000000405
Cai Z, Jiang X, Pan Y et al. Transcriptomic analysis of hepatic responses to testosterone deficiency in miniature pigs fed a high cholesterol diet. BMC Genomics. 2015; 16:59. DOI: https://doi.org/10.1186/s12864-015-1283-0
Lee KS, Kim HP, Park HJ, Yoon YG. Improvement of testosterone deficiency by fermented Momordica charantia extracts in aging male rats. Food Sci Biotechnol. 2021; 30:443. DOI: https://doi.org/10.1007/s10068-020-00872-x
Pereira ACM, de Oliveira Carvalho H, Gonçalves DES, et al. Cotreatment of purified annatto oil (Bixa orellana L.) and its granules improves the blood lipid profile and bone protective effects of testosterone in the orchiectomy-induced osteoporosis in Wistar Rats. Molecules. 2021; 26:4720. DOI: https://doi.org/10.3390/molecules26164720
Vodo, S, Bechi N, Petroni A, et al. Testosterone-induced effects on lipids and inflammation. Mediators Inflamm. 2013; 2013:183041. DOI: https://doi.org/10.1155/2013/183041
Yuefeng Y, Zhiqi L, Yi C, et al. Testosterone Deficiency Promotes Hypercholesteremia and Attenuates Cholesterol Liver Uptake via AR/PCSK9/LDLR Pathways. Int J Endocrinol. 2022; 1. DOI: https://doi.org/10.1155/2022/7989751
Nikolaenko L, Jia Y, Wang C, et al. Testosterone replacement ameliorates nonalcoholic fatty liver disease in castrated male rats. Endocrinology. 2014; 155:417. DOI: https://doi.org/10.1210/en.2013-1648
Hua P, Yu Z, Xiong Y, Liu B, Zhao L. Regulatory Efficacy of Spirulina platensis Protease Hydrolyzate on Lipid Metabolism and Gut Microbiota in High-Fat Diet-Fed Rats. Int J Mol Sci. 2018; 19:4023. DOI: https://doi.org/10.3390/ijms19124023
Alani F, Alizadeh M, Shateri K. The effect of fruit-rich diet on liver biomarkers, insulin resistance, and lipid profile in patients with non-alcoholic fatty liver disease: a randomized clinical trial. Scand J Gastroenterol. 2022; 10:1238. DOI: https://doi.org/10.1080/00365521.2022.2071109
Demirci-çekik S, Özkao G, Avan AN, et al. Biomarkers of oxidative stress and antioxidant defense. J Pharm Biomed Anal. 2022; 205:114477. DOI: https://doi.org/10.1016/j.jpba.2021.114477
Liguori I, Russo G, Curcio F, et al. Oxidative stress, aging, and diseases. Clinical Interventions in Aging. 2018; 13:757. DOI: https://doi.org/10.2147/CIA.S158513
Teleanu DM, Niculescu AG, Lungu II, et al. An overwiew of oxidative stress, neuroinflammation, and neurodegenerative diseases. Int J Mol Sci. 2022; 23:5938. DOI: https://doi.org/10.3390/ijms23115938
Mancini A, Leone E, Festa R, et al. Effects of testosterone on antioxidant systems in male secondary hypogonadism. J Androl. 2008; 29:622. DOI: https://doi.org/10.2164/jandrol.107.004838
Hwang TI, Liao TL, Lin JF, et al. Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells. Asian J Androl. 2011; 13:432. DOI: https://doi.org/10.1038/aja.2010.159
Montaño-González RI, Gutiérrez-Salmeán G, Mojica-Villegas MA, et al. Phycobiliproteins extract from Spirulina protects against single-dose cadmium-induced reproductive toxicity in male mice. Environ Sci Pollut Res Int. 2022; 29:17441. DOI: https://doi.org/10.1007/s11356-021-16668-3
Giagulli V, Guastamacchia E, Licchelli B, Triggiani V. Serum Testosterone and Cognitive Function in Ageing Male: Updating the Evidence. Recent Prat. Endocr Metab Immune Drug Discov. 2016; 10:22. DOI: https://doi.org/10.2174/1872214810999160603213743
Khakpai F. The effect of opiodergic system and testosterone on anxiety behavior in gonadectomized rats. Beha. Brain Res. 2014; 263:9. DOI: https://doi.org/10.1016/j.bbr.2014.01.013
Frye CA, Edinger KL, Lephart ED, Walf AA. 3alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats. Front Aging Neurosci. 2010; 8:2. DOI: https://doi.org/10.3389/fnagi.2010.00015
Durdiakova J, Ostatnikova D, Celec P. Testosterone and its metabolites--modulators of brain functions. Acta Neurobiol. Exp. 2011; 71:434.
Pintana H, Pongkan W, Pratchayasakul W, et al. Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats, but not in obese rats, by mitigating brain oxidative stress. AGE. 2015; 37:84. DOI: https://doi.org/10.1007/s11357-015-9827-4
Borbélyová V, Domonkos E, Bábícková J, et al. No effect of testosterone on behavior in aged Wistar rats. Aging. 2016; 8:2848. DOI: https://doi.org/10.18632/aging.101096
Ghanbari A, Vafaei AA, Naghibi Nasab FS, et al. Spirulina microalgae improves memory deficit induced by scopolamine in male pup rats: Role of oxidative stress. S Afr J Bot. 2019; 127:220. DOI: https://doi.org/10.1016/j.sajb.2019.08.045
Wang P, Wang Y, Zhang Q, et al. Amelioration of cognitive deficits by Spirulina platensis in L-methionine-induced rat model of vascular dementia. Pharmacogn Mag. 2020; 16:133. DOI: https://doi.org/10.4103/pm.pm_438_19

How to Cite

Boukari, O., Khemissi, W., Ghodhbane, S., Lahbib, A., Tebourbi, O., Rhouma, K. B., Sakly, M., & Hallegue, D. (2023). Effects of testosterone replacement on lipid profile, hepatotoxicity, oxidative stress, and cognitive performance in castrated wistar rats. Archivio Italiano Di Urologia E Andrologia, 95(4). https://doi.org/10.4081/aiua.2023.11593