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Kumar Netam, A., Pankaj Bhargava, V., Singh, R., & Sharma, P. (2023). Testosterone propionate and Swarna Bhasma treatment modulated D-galactose induced reproductive alterations in male Wistar rats: An experimental study. International Journal of Reproductive BioMedicine (IJRM), 21(4), 303–322. https://doi.org/10.18502/ijrm.v21i4.13270
https://doi.org/10.18502/ijrm.v21i4.13270
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authors
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Aashish Kumar Netam
Aashish Kumar Netam
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India.
-
Vikas Pankaj Bhargava
Vikas Pankaj Bhargava
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India.
-
Rambir Singh
Rambir Singh
Department of Horticulture, Aromatic and Medicinal Plants, Mizoram University, Aizawl, Mizoram, India.
-
Poonam Sharma
Poonam Sharma
Department of Zoology, Indira Gandhi National Tribal University, Amarkantak, Madhya Pradesh, India.
Published Date
- May 6, 2023
Testosterone propionate and Swarna Bhasma treatment modulated D-galactose induced reproductive alterations in male Wistar rats: An experimental study
Abstract
Background: The male reproductive system undergoes several adverse age-related changes like decreased hormone synthesis, sperm count, and testicular alteration that can impact on fertility.
Objective: The study aims to investigate the effects of testosterone propionate (TP), and ayurvedic formulation Swarna Bhasma (SB) on D-galactose (D-gal) induced reproductive aging in male Wistar rats.
Materials and Methods: 60 male Wistar rats were divided into 10 groups of 6 animals. Reproductive aging was induced by D-gal (150 mg/kg Bwt) exposure for 60 days. The rats were then treated by post and combination treatment with TP (2 mg/kg Bwt) and SB (6.75 mg/kg Bwt). Then sperm parameters, reproductive hormones, inflammatory markers, testicular antioxidant enzymes, steroidogenic enzymes, and histological manifestation of testis were evaluated.
Results: Exposure of D-gal caused significant (p < 0.001) decrease in serum testosterone (T), testicular steroidogenic, and antioxidant enzymes. Administration of TP increased the serum T level, testicular antioxidant enzymes, and spermatogenic profile at a significant level of (p < 0.001) compared to D-gal. Further, the SB treatment significantly (p < 0.001) elevated the serum T level, sperm count, testicular antioxidant enzymes, steroidogenic enzymes, when compared to D-gal.
Conclusion: Both the treatment of TP and SB treatments recovered the reproductive impairments caused by D-gal. However, exogenous T supplementation via TP administration is associated with various side effects during long-term use. SB is an Ayurvedic formulation having a long history of usage in India. The current findings suggest that the SB may be used as a good alternative for potentiating reproductive function in aging males.
Key words: D-galactose, Aging, Testosterone propionate, Swarna Bhasma, Testis, Hypogonadism, infertility.
References
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[2] Gunes S, Hekim GNT, Arslan MA, Asci R. Effects of aging on the male reproductive system. J Assist Reprod Genet 2016; 33: 441–454.
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[4] Liao C-H, Chen B-H, Chiang H-S, Chen C-W, Chen M-F, Ke C-C, et al. Optimizing a male reproductive aging mouse model by d-galactose injection. Int J Mol Sci 2016; 17: 98.
[5] Sulistyoningrum E. D-galactose induced animal model of male reproductive aging. Jurnal Kedokteran dan Kesehatan Indonesia 2017; 8: 19–27.
[6] Ahangarpour A, Oroojan AA, Heidari H. Effects of exendin 4 on male reproductive parameters of D-galactose induced aging mouse model world. World J Mens Health 2014; 32: 176–183.
[7] Nassar GN, Leslie SW. Physiology Testosterone. In: StatPearls. StatPearls Publishing; 2022.
[8] Rey RA. Recent advancement in the treatment of boys and adolescents with hypogonadism. Ther Adv Endocrinol Metab 2022; 13: 20420188211065660.
[9] Sharma A, Minhas S, Dhillo WS, Jayasena CN. Male infertility due to testicular disorders. J Clin Endocrinol Metab 2021; 106: e442–e459.
[10] Walker WH. Androgen actions in the testis and the regulation of spermatogenesis. Adv Exp Med Biol 2021; 1288: 175–203.
[11] Chioma L, Cappa M. Hypogonadism in male infants and adolescents: New androgen formulations. Horm Res Paediatr 2021; 1–9.
[12] Suarez AMC, Israeli JM, Kresch E, Telis L, Nassau DE. Testosterone therapy in children and adolescents: To whom how when? Int J Impot Res 2022; 34: 652–662.
[13] Rizk PJ, Kohn TP, Pastuszak AW, Khera M. Testosterone therapy improves erectile function and libido in hypogonadal men. Curr Opin Urol 2017; 27: 511–515.
[14] Yabluchanskiy A, Tsitouras PD. Is testosterone replacement therapy in older men effective and safe? Drugs Aging 2019; 36: 981–989.
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[17] Khodamoradi K, Khosravizadeh Z, Parmar M, Kuchakulla M, Ramasamy R, Arora H. Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: Current and future prospects. F S Rev 2021; 2: 32–42.
[18] Rahimi A, Asadi F, Rezghi M, Kazemi S, Soorani F, Memariani Z. Natural products against cisplatin induced male reproductive toxicity: A comprehensive review. J Biochem Mol Toxicol 2022; 36: e22970.
[19] Beaudet D, Badilescu S, Kuruvinashetti K, Sohrabi Kashani A, Jaunky D, Ouellette S, et al. Comparative study on cellular entry of incinerated ancient gold particles (Swarna Bhasma) and chemically synthesized gold particles. Sci Rep 2017; 7: 10678.
[20] Patel MK, Archana L, Netam N, Parhate S. Vasantkusumakar rasa - “a best antidiabetic drug in modern era”: A review. Int Ayurvedic Med J 2018; 6: 2305–2311.
[21] Singh BN, Prateeksha P, Pandey G, Jadaun V, Singh S, Bajpai R, et al. Development, and characterization of a novel Swarna based herbo metallic colloidal nano formulation-inhibitor of Streptococcus mutans quorum sensing. RSC Adv 2015; 5: 5809–5822.
[22] Yadav KD. Percentage of Swarna Bhasma in medicaments of Ayurveda to treat disorders of different origin. Int J Green Pharm 2015; 9: 90–94.
[23] Cui R, Kang Y, Wang L, Li S, Ji X, Yan W, et al. Testosterone propionate exacerbates the deficits of nigrostriatal dopaminergic system and downregulates Nrf2 expression in reserpinetreated aged male rats. Front Aging Neurosci 2017; 9: 172.
[24] Jamadagni PS, Jamadagni SB, Singh A, Kumar Singh R, Upadhyay SN, Gaidhani SN, et al. Toxicity study of Swarna Bhasma, an ayurvedic medicine containing gold, in wistar rats. Toxicol Int 2015; 22: 11–17.
[25] Widyastuti R, Prastowo S, Sumarsono SH, Lubis A, Hartady T, Syamsunarno MRAA, et al. Deleterious effect of short-term gavage of an ethanol extract of cogon grass (Imperata cylindrica L.) roots on testis and epididymal sperm quality. Vet World 2020; 13: 1311–1318.
[26] Aksu EH, Kandemir FM, Kucukler S. Ameliorative effect of hesperidin on streptozotocin diabetes mellitus induced testicular DNA damage and sperm quality degradation in Sprague-Dawley rats. J Food Biochem 2021; 45: e13938.
[27] Selmi S, Tounsi H, Safra I, Abdellaoui A, Rjeibi MR, El-Fazaa S, et al. Histopathological biochemical and molecular changes of reproductive function after malathion exposure of prepubertal male mice. RSC Adv 2015; 5: 13743–13753.
[28] Bhattacharjee A, Shashidhara SC, Saha S. Neuroprotective activity of Crataeva nurvala buch ham stem bark against scopolamine induced cognitive impairment via antioxidative activities in rats. Am J Ethnomed 2014; 1: 371–383.
[29] Mohammadi E, Zeinali M, Mohammadi-Sardoo M, Iranpour M, Behnam B, Mandegary A. The effects of functionalization of carbon nanotubes on toxicological parameters in mice. Hum Exp Toxicol 2020; 39: 1147–1167.
[30] Grami D, Rtibi K, Hammami I, Selmi S, Toni LD, Foresta C, et al. Protective action of Eruca sativa leaves aqueous extracts against bisphenol A-caused in vivo testicular damages. J Med Food 2020; 23: 600-610.
[31] Shah NA, Khan MR. Increase of glutathione testosterone and antioxidant effects of Jurenia dolomiaea on CCl4 induced testicular toxicity in rat. BMC Complement Altern Med 2017; 17: 206.
[32] Kielkopf CL, Bauer W, Urbatsch IL. Methods for measuring the concentrations of proteins. Cold Spring Harb Protoc 2020: 102277.
[33] Iglesias P, Prado F, Díez JJ. Male hypogonadism and aging. In: Hohl A. Testosterone. Switzerland: Springer; 2017.
[34] Shaikh NH, Deshmukh VM, Walvekar MV. Alteration in testicular morphology and sperm count due to glycowithanolides treatment during aging. Asian J Pharm Clin Res 2015; 8: 72–77.
[35] Zhang Q, Yang C, Zhang M, Lu X, Cao W, Xie C, et al. Protective effects of ginseng stem leaf saponins on D-galactose induced reproductive injury in male mice. Aging 2021; 13: 8916–8928.
[36] Wang F, Zhou H, Deng L, Wang L, Chen J, Zhou X, et al. Serine deficiency exacerbates inflammation and oxidative stress via microbiota gut brain axis in DGalactose induced aging mice. Mediators Inflamm 2020; 2020: 5821428.
[37] Taba MY, Mohammadi Sh, Jalali M, Beheshti F, Attari SS. Effects of different doses of curcumin on testicular histopathology apoptosis and reproductive organs weight index in mice d galactose induced aging model. Comp Clin Pathol 2019; 28: 997–1002.
[38] Jeremy M, Gurusubramanian G, Roy V, Kharwar RK. Co treatment of testosterone and estrogen mitigates heat induced testicular dysfunctions in a rat model. J Steroid Biochem Mol Biol 2021; 214: 106011.
[39] Wang N, Xu Y, Zhou X-Q, Wu Y-H, Li S-L, Qiao X, et al. Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice. Environ Toxicol 2016; 31: 142–153.
[40] Makary S, Abdo M, Fekry E. Oxidative stress burden inhibits spermatogenesis in adult male rats: Testosterone protective effect. Can J Physiol Pharmacol 2018; 96: 372–381.
[41] Skandhan KP, Manesh EN, Singh G, Rao N, Prasad BS. Effect of “Suvarna Bhasma” (Gold Ash) an indigenous ayurvedic preparation on human sperm motility. JSM Sex Med 2017; 2: 1009.
[42] Subramaniyan Parimalam S, Badilescu S, Bhat R, Packirisamy M. A narrative review of scientific validation of gold and silver based Indian medicines and their future scope. Longhua Chin Med 2020; 3: 1–14.
[43] Netam AK, Bhargava VP, Singh R, Sharma P. Physico chemical characterization of ayurvedic Swarna Bhasma by using SEM, EDAX, XRD and PSA. J Complement Med Res 2021; 12: 204–209.
[2] Gunes S, Hekim GNT, Arslan MA, Asci R. Effects of aging on the male reproductive system. J Assist Reprod Genet 2016; 33: 441–454.
[3] Kaufman J-M, Lapauw B, Mahmoud A, T’Sjoen G, Huhtaniemi IT. Aging and the male reproductive system. Endocr Rev 2019; 40: 906–972.
[4] Liao C-H, Chen B-H, Chiang H-S, Chen C-W, Chen M-F, Ke C-C, et al. Optimizing a male reproductive aging mouse model by d-galactose injection. Int J Mol Sci 2016; 17: 98.
[5] Sulistyoningrum E. D-galactose induced animal model of male reproductive aging. Jurnal Kedokteran dan Kesehatan Indonesia 2017; 8: 19–27.
[6] Ahangarpour A, Oroojan AA, Heidari H. Effects of exendin 4 on male reproductive parameters of D-galactose induced aging mouse model world. World J Mens Health 2014; 32: 176–183.
[7] Nassar GN, Leslie SW. Physiology Testosterone. In: StatPearls. StatPearls Publishing; 2022.
[8] Rey RA. Recent advancement in the treatment of boys and adolescents with hypogonadism. Ther Adv Endocrinol Metab 2022; 13: 20420188211065660.
[9] Sharma A, Minhas S, Dhillo WS, Jayasena CN. Male infertility due to testicular disorders. J Clin Endocrinol Metab 2021; 106: e442–e459.
[10] Walker WH. Androgen actions in the testis and the regulation of spermatogenesis. Adv Exp Med Biol 2021; 1288: 175–203.
[11] Chioma L, Cappa M. Hypogonadism in male infants and adolescents: New androgen formulations. Horm Res Paediatr 2021; 1–9.
[12] Suarez AMC, Israeli JM, Kresch E, Telis L, Nassau DE. Testosterone therapy in children and adolescents: To whom how when? Int J Impot Res 2022; 34: 652–662.
[13] Rizk PJ, Kohn TP, Pastuszak AW, Khera M. Testosterone therapy improves erectile function and libido in hypogonadal men. Curr Opin Urol 2017; 27: 511–515.
[14] Yabluchanskiy A, Tsitouras PD. Is testosterone replacement therapy in older men effective and safe? Drugs Aging 2019; 36: 981–989.
[15] Desroches B, Kohn TP, Welliver C, Pastuszak AW. Testosterone therapy in the new era of food and drug administration oversight. Transl Androl Urol 2016; 5: 207–212.
[16] Linhares BL, Miranda EP, Cintra AR, Reges R, Torres LO. Use misuse and abuse of testosterone and other androgens. Sex Med Rev 2022; 10: 583–595.
[17] Khodamoradi K, Khosravizadeh Z, Parmar M, Kuchakulla M, Ramasamy R, Arora H. Exogenous testosterone replacement therapy versus raising endogenous testosterone levels: Current and future prospects. F S Rev 2021; 2: 32–42.
[18] Rahimi A, Asadi F, Rezghi M, Kazemi S, Soorani F, Memariani Z. Natural products against cisplatin induced male reproductive toxicity: A comprehensive review. J Biochem Mol Toxicol 2022; 36: e22970.
[19] Beaudet D, Badilescu S, Kuruvinashetti K, Sohrabi Kashani A, Jaunky D, Ouellette S, et al. Comparative study on cellular entry of incinerated ancient gold particles (Swarna Bhasma) and chemically synthesized gold particles. Sci Rep 2017; 7: 10678.
[20] Patel MK, Archana L, Netam N, Parhate S. Vasantkusumakar rasa - “a best antidiabetic drug in modern era”: A review. Int Ayurvedic Med J 2018; 6: 2305–2311.
[21] Singh BN, Prateeksha P, Pandey G, Jadaun V, Singh S, Bajpai R, et al. Development, and characterization of a novel Swarna based herbo metallic colloidal nano formulation-inhibitor of Streptococcus mutans quorum sensing. RSC Adv 2015; 5: 5809–5822.
[22] Yadav KD. Percentage of Swarna Bhasma in medicaments of Ayurveda to treat disorders of different origin. Int J Green Pharm 2015; 9: 90–94.
[23] Cui R, Kang Y, Wang L, Li S, Ji X, Yan W, et al. Testosterone propionate exacerbates the deficits of nigrostriatal dopaminergic system and downregulates Nrf2 expression in reserpinetreated aged male rats. Front Aging Neurosci 2017; 9: 172.
[24] Jamadagni PS, Jamadagni SB, Singh A, Kumar Singh R, Upadhyay SN, Gaidhani SN, et al. Toxicity study of Swarna Bhasma, an ayurvedic medicine containing gold, in wistar rats. Toxicol Int 2015; 22: 11–17.
[25] Widyastuti R, Prastowo S, Sumarsono SH, Lubis A, Hartady T, Syamsunarno MRAA, et al. Deleterious effect of short-term gavage of an ethanol extract of cogon grass (Imperata cylindrica L.) roots on testis and epididymal sperm quality. Vet World 2020; 13: 1311–1318.
[26] Aksu EH, Kandemir FM, Kucukler S. Ameliorative effect of hesperidin on streptozotocin diabetes mellitus induced testicular DNA damage and sperm quality degradation in Sprague-Dawley rats. J Food Biochem 2021; 45: e13938.
[27] Selmi S, Tounsi H, Safra I, Abdellaoui A, Rjeibi MR, El-Fazaa S, et al. Histopathological biochemical and molecular changes of reproductive function after malathion exposure of prepubertal male mice. RSC Adv 2015; 5: 13743–13753.
[28] Bhattacharjee A, Shashidhara SC, Saha S. Neuroprotective activity of Crataeva nurvala buch ham stem bark against scopolamine induced cognitive impairment via antioxidative activities in rats. Am J Ethnomed 2014; 1: 371–383.
[29] Mohammadi E, Zeinali M, Mohammadi-Sardoo M, Iranpour M, Behnam B, Mandegary A. The effects of functionalization of carbon nanotubes on toxicological parameters in mice. Hum Exp Toxicol 2020; 39: 1147–1167.
[30] Grami D, Rtibi K, Hammami I, Selmi S, Toni LD, Foresta C, et al. Protective action of Eruca sativa leaves aqueous extracts against bisphenol A-caused in vivo testicular damages. J Med Food 2020; 23: 600-610.
[31] Shah NA, Khan MR. Increase of glutathione testosterone and antioxidant effects of Jurenia dolomiaea on CCl4 induced testicular toxicity in rat. BMC Complement Altern Med 2017; 17: 206.
[32] Kielkopf CL, Bauer W, Urbatsch IL. Methods for measuring the concentrations of proteins. Cold Spring Harb Protoc 2020: 102277.
[33] Iglesias P, Prado F, Díez JJ. Male hypogonadism and aging. In: Hohl A. Testosterone. Switzerland: Springer; 2017.
[34] Shaikh NH, Deshmukh VM, Walvekar MV. Alteration in testicular morphology and sperm count due to glycowithanolides treatment during aging. Asian J Pharm Clin Res 2015; 8: 72–77.
[35] Zhang Q, Yang C, Zhang M, Lu X, Cao W, Xie C, et al. Protective effects of ginseng stem leaf saponins on D-galactose induced reproductive injury in male mice. Aging 2021; 13: 8916–8928.
[36] Wang F, Zhou H, Deng L, Wang L, Chen J, Zhou X, et al. Serine deficiency exacerbates inflammation and oxidative stress via microbiota gut brain axis in DGalactose induced aging mice. Mediators Inflamm 2020; 2020: 5821428.
[37] Taba MY, Mohammadi Sh, Jalali M, Beheshti F, Attari SS. Effects of different doses of curcumin on testicular histopathology apoptosis and reproductive organs weight index in mice d galactose induced aging model. Comp Clin Pathol 2019; 28: 997–1002.
[38] Jeremy M, Gurusubramanian G, Roy V, Kharwar RK. Co treatment of testosterone and estrogen mitigates heat induced testicular dysfunctions in a rat model. J Steroid Biochem Mol Biol 2021; 214: 106011.
[39] Wang N, Xu Y, Zhou X-Q, Wu Y-H, Li S-L, Qiao X, et al. Protective effects of testosterone propionate on reproductive toxicity caused by Endosulfan in male mice. Environ Toxicol 2016; 31: 142–153.
[40] Makary S, Abdo M, Fekry E. Oxidative stress burden inhibits spermatogenesis in adult male rats: Testosterone protective effect. Can J Physiol Pharmacol 2018; 96: 372–381.
[41] Skandhan KP, Manesh EN, Singh G, Rao N, Prasad BS. Effect of “Suvarna Bhasma” (Gold Ash) an indigenous ayurvedic preparation on human sperm motility. JSM Sex Med 2017; 2: 1009.
[42] Subramaniyan Parimalam S, Badilescu S, Bhat R, Packirisamy M. A narrative review of scientific validation of gold and silver based Indian medicines and their future scope. Longhua Chin Med 2020; 3: 1–14.
[43] Netam AK, Bhargava VP, Singh R, Sharma P. Physico chemical characterization of ayurvedic Swarna Bhasma by using SEM, EDAX, XRD and PSA. J Complement Med Res 2021; 12: 204–209.