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Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | Hyperprolactinemia | Research article

Cannabinoid-deficient Benin republic hemp (Cannabis sativa L.) improves semen parameters by reducing prolactin and enhancing anti-oxidant status

Authors: Abdullateef Isiaka Alagbonsi, Luqman Aribidesi Olayaki, Halimat Amin Abdulrahim, Thomson Sijuade Adetona, Gbemileke Tobiloba Akinyemi

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

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Abstract

Background

Nigerian Cannabis sativa (hemp) causes male gonadotoxicity by inducing hyperprolactinemia, down-regulation of hypothalamic-pituitary-testicular axis, and oxidative stress. Benin republic hemp has been preferred by illicit users in Nigeria but its effect on male fertility is not understood. This study determined and compared the compositions of Benin republic hemp ethanol extract (BHE) and Nigerian hemp. The effects of BHE on semen parameters, reproductive hormones, and anti-oxidant status, and the possibility of bromocriptine (prolactin inhibitor) to abolish hemp-induced toxicities in rats were also investigated.

Methods

Thirty-six male Wistar rats were blindly randomized into 6 oral treatment groups (n = 6 each). Groups I (control) and II received normal saline and bromocriptine (3 mg/kg) respectively. Groups III and IV received 2 mg/kg of BHE alone and in combination with bromocriptine respectively, while groups V and VI received 10 mg/kg BHE alone and in combination with bromocriptine respectively. Comparisons among the groups were done by one-way analysis of variance, followed by post-hoc Tukey multiple comparison test. Statistical significance was considered at p < 0.05.

Results

The BHE has no cannabichromene and tetrahydrocannabinol but a very small quantity of cannabinol and higher quantity of fatty acids when compared to Nigerian hemp. Both doses of BHE increased sperm count, morphology and viability but not motility. Co-administration of BHE with bromocriptine lowered sperm count but increased sperm morphology and viability. Bromocriptine and/or BHE caused reduction in the plasma prolactin level, increase in the plasma superoxide dismutase activity, but no significant change in the plasma gonadotropin releasing hormone, follicle stimulating hormone (except for the increase in rats that received bromocriptine+ 10 mg/kg BHE), luteinizing hormone, estradiol, malondialdehyde and glutathione peroxidase. The 10 mg/kg BHE or bromocriptine+BHE (both doses) increased total anti-oxidant capacity and catalase.

Conclusions

The BHE improves semen parameters by reducing plasma prolactin and enhancing plasma anti-oxidant status. Its pro-fertility potential might be associated with its deficiency in the widely known gonadotoxic phytocannabinoids.
Literature
1.
go back to reference Abdel-Salam O. Gastric acid inhibitory and gastric protective effects of cannabis and cannabinoids. Asian Pac J Trop Med. 2016;9(5):413–9.PubMedCrossRef Abdel-Salam O. Gastric acid inhibitory and gastric protective effects of cannabis and cannabinoids. Asian Pac J Trop Med. 2016;9(5):413–9.PubMedCrossRef
2.
go back to reference Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure. 2016;35:41–4.PubMedCrossRef Tzadok M, Uliel-Siboni S, Linder I, Kramer U, Epstein O, Menascu S, Nissenkorn A, Yosef OB, Hyman E, Granot D, et al. CBD-enriched medical cannabis for intractable pediatric epilepsy: the current Israeli experience. Seizure. 2016;35:41–4.PubMedCrossRef
3.
go back to reference Juknat A, Kozela E, Kaushansky N, Mechoulam R, Vogel Z. Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells. J Basic Clin Physiol Pharmacol. 2016;27(3):289–96.PubMedCrossRef Juknat A, Kozela E, Kaushansky N, Mechoulam R, Vogel Z. Anti-inflammatory effects of the cannabidiol derivative dimethylheptyl-cannabidiol – studies in BV-2 microglia and encephalitogenic T cells. J Basic Clin Physiol Pharmacol. 2016;27(3):289–96.PubMedCrossRef
4.
go back to reference Velasco G, Hernandez-Tiedra S, Davila D, Lorente M. The use of cannabinoids as anticancer agents. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;64:259–66.CrossRef Velasco G, Hernandez-Tiedra S, Davila D, Lorente M. The use of cannabinoids as anticancer agents. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;64:259–66.CrossRef
5.
go back to reference Lynch ME. Cannabinoids in the management of chronic pain: a front-line clinical perspective. J Basic Clin Physiol Pharmacol. 2016;27(3):189–91.PubMedCrossRef Lynch ME. Cannabinoids in the management of chronic pain: a front-line clinical perspective. J Basic Clin Physiol Pharmacol. 2016;27(3):189–91.PubMedCrossRef
6.
go back to reference Lazzari P, Serra V, Marcello S, Pira M, Mastinu A. Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds con-administration in female rats. Eur Neuropsycopharmacol. 2017;27(7):667–78.CrossRef Lazzari P, Serra V, Marcello S, Pira M, Mastinu A. Metabolic side effects induced by olanzapine treatment are neutralized by CB1 receptor antagonist compounds con-administration in female rats. Eur Neuropsycopharmacol. 2017;27(7):667–78.CrossRef
7.
go back to reference Alagbonsi IA, Olayaki LA. Melatonin attenuates ∆9-tetrahydrocannabinol-induced reduction in rat sperm motility and kinematics in-vitro. Reprod Toxicol. 2018;77:62–9.PubMedCrossRef Alagbonsi IA, Olayaki LA. Melatonin attenuates ∆9-tetrahydrocannabinol-induced reduction in rat sperm motility and kinematics in-vitro. Reprod Toxicol. 2018;77:62–9.PubMedCrossRef
8.
go back to reference Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, Mastinu A. Cannabis sativa: a comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol. 2018;227:300–15.PubMedCrossRef Bonini SA, Premoli M, Tambaro S, Kumar A, Maccarinelli G, Memo M, Mastinu A. Cannabis sativa: a comprehensive ethnopharmacological review of a medicinal plant with a long history. J Ethnopharmacol. 2018;227:300–15.PubMedCrossRef
9.
go back to reference Gundersen TS, Jorgensen N, Andersson A, Bang AK, Nordkap L, Shakkebak NE, Priskorn L, Juul A, Jensen TK. Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men. Am J Epidemiol. 2015;182(6):473–81.PubMedCrossRef Gundersen TS, Jorgensen N, Andersson A, Bang AK, Nordkap L, Shakkebak NE, Priskorn L, Juul A, Jensen TK. Association between use of marijuana and male reproductive hormones and semen quality: a study among 1,215 healthy young men. Am J Epidemiol. 2015;182(6):473–81.PubMedCrossRef
10.
go back to reference Alagbonsi IA, Olayaki LA, Salman TM. Melatonin and vitamin C exacerbate Cannabis sativa-induced testicular damage when administered separately but ameliorate it when combined in rats. J Basic Clin Physiol Pharmacol. 2016;27(3):277–87.PubMedCrossRef Alagbonsi IA, Olayaki LA, Salman TM. Melatonin and vitamin C exacerbate Cannabis sativa-induced testicular damage when administered separately but ameliorate it when combined in rats. J Basic Clin Physiol Pharmacol. 2016;27(3):277–87.PubMedCrossRef
11.
go back to reference Alagbonsi IA, Olayaki LA. Role of oxidative stress in Cannabis sativa-associated spermatotoxicity: evidence for ameliorative effect of combined but not separate melatonin and vitamin C. Middle East Fertil Soc J. 2017;22(2):136–44.CrossRef Alagbonsi IA, Olayaki LA. Role of oxidative stress in Cannabis sativa-associated spermatotoxicity: evidence for ameliorative effect of combined but not separate melatonin and vitamin C. Middle East Fertil Soc J. 2017;22(2):136–44.CrossRef
12.
go back to reference Cobellis G, Cacciola G, Scarpa D, Meccariello R, Chianese R, Franzoni MF, Mackie K, Pierantoni R, Fasano S. Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Biol Reprod. 2006;75(1):82–9.PubMedCrossRef Cobellis G, Cacciola G, Scarpa D, Meccariello R, Chianese R, Franzoni MF, Mackie K, Pierantoni R, Fasano S. Endocannabinoid system in frog and rodent testis: type-1 cannabinoid receptor and fatty acid amide hydrolase activity in male germ cells. Biol Reprod. 2006;75(1):82–9.PubMedCrossRef
13.
go back to reference Alagbonsi IA, Olayaki LA. Ameliorative effect of combined melatonin and vitamin C on Cannabis sativa-induced reproductive hormonal toxicity. J Afr Ass Physiol Sci. 2016;4(1):14–24. Alagbonsi IA, Olayaki LA. Ameliorative effect of combined melatonin and vitamin C on Cannabis sativa-induced reproductive hormonal toxicity. J Afr Ass Physiol Sci. 2016;4(1):14–24.
14.
go back to reference El-Habashi AA, Mousa MA, El-Eraky WI, Khalil WKB, Ahmed HH, Moad MAA. Possible mechanisms for the toxic effects of marijuana smoke on the reproductive axis of male albino rats. J Appl Pharm Sci. 2013;3(4):S59–67. El-Habashi AA, Mousa MA, El-Eraky WI, Khalil WKB, Ahmed HH, Moad MAA. Possible mechanisms for the toxic effects of marijuana smoke on the reproductive axis of male albino rats. J Appl Pharm Sci. 2013;3(4):S59–67.
15.
go back to reference Masud S, Mehboob F, Bappi MU. Severe hyperprolactinemia directly depresses the gonadal activity causing infertility. Esculapio J Services Inst Med Sci. 2007;2(4):25–7. Masud S, Mehboob F, Bappi MU. Severe hyperprolactinemia directly depresses the gonadal activity causing infertility. Esculapio J Services Inst Med Sci. 2007;2(4):25–7.
16.
go back to reference Soler Fernández JM, Caravaca Magariños F, Domínguez Bravo C, Murillo Mirat J, Aparicio Palomino A, Herrera Puerto J. Correlation of serum prolactin, sperm count and motility. Prevalence of hyperprolactinemia in the infertile male. Arch Esp Urol. 1990;43(8):891–5.PubMed Soler Fernández JM, Caravaca Magariños F, Domínguez Bravo C, Murillo Mirat J, Aparicio Palomino A, Herrera Puerto J. Correlation of serum prolactin, sperm count and motility. Prevalence of hyperprolactinemia in the infertile male. Arch Esp Urol. 1990;43(8):891–5.PubMed
17.
go back to reference Buvat J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15(5):373–7.PubMedCrossRef Buvat J. Hyperprolactinemia and sexual function in men: a short review. Int J Impot Res. 2003;15(5):373–7.PubMedCrossRef
18.
go back to reference De Rosa M, Zarrilli S, Di Sarno A, Milano N, Gaccione M, Boggia B, Lombardi G, Colao A. Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine. 2003;20(1–2):75–82.PubMedCrossRef De Rosa M, Zarrilli S, Di Sarno A, Milano N, Gaccione M, Boggia B, Lombardi G, Colao A. Hyperprolactinemia in men: clinical and biochemical features and response to treatment. Endocrine. 2003;20(1–2):75–82.PubMedCrossRef
19.
go back to reference Laufer N, Yaffe H, Margalioth EJ, Livshin J, Ben-David M, Schenker JG. Effect of bromocriptine treatment on male infertility associated with hyperprolactinemia. Arch Androl. 1981;6(4):343–6.PubMedCrossRef Laufer N, Yaffe H, Margalioth EJ, Livshin J, Ben-David M, Schenker JG. Effect of bromocriptine treatment on male infertility associated with hyperprolactinemia. Arch Androl. 1981;6(4):343–6.PubMedCrossRef
20.
go back to reference Mandal TK, Das NS. Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of anti-oxidant systems. Toxicol Ind Health. 2010;26(1):11–23.PubMedCrossRef Mandal TK, Das NS. Testicular toxicity in cannabis extract treated mice: association with oxidative stress and role of anti-oxidant systems. Toxicol Ind Health. 2010;26(1):11–23.PubMedCrossRef
21.
go back to reference Dall’Ara A, Lima L, Cocchi D, Di Salle E, Cancio E, Devesa J, Muller EE. Inhibitory effect of cabergoline on the development of estrogen-induced prolactin-secreting adenomas of the pituitary. Eur J Pharmacol. 1988;151(1):97–102.PubMedCrossRef Dall’Ara A, Lima L, Cocchi D, Di Salle E, Cancio E, Devesa J, Muller EE. Inhibitory effect of cabergoline on the development of estrogen-induced prolactin-secreting adenomas of the pituitary. Eur J Pharmacol. 1988;151(1):97–102.PubMedCrossRef
22.
go back to reference Abdel-Salam OME, El-Shamarka ME, Salem NA, Gaafar AEM. Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice. EXCLI J. 2012;11:45–58.PubMedPubMedCentral Abdel-Salam OME, El-Shamarka ME, Salem NA, Gaafar AEM. Effects of Cannabis sativa extract on haloperidol-induced catalepsy and oxidative stress in the mice. EXCLI J. 2012;11:45–58.PubMedPubMedCentral
23.
go back to reference Salman TM, Olayaki LA, Alagbonsi IA, Oyewopo AO. Spermatotoxic effect of galactose and possible mechanism of action. Middle East Fertil Soc J. 2016;21(2):82–90.CrossRef Salman TM, Olayaki LA, Alagbonsi IA, Oyewopo AO. Spermatotoxic effect of galactose and possible mechanism of action. Middle East Fertil Soc J. 2016;21(2):82–90.CrossRef
24.
go back to reference Olayaki LA, Alagbonsi IA, Abdulkadir HO, Idowu FO. Low dose of melatonin ameliorates cryptorchidism-induced spermatotoxicity in rats. J Anat Soc India. 2017;66(1):67–71.CrossRef Olayaki LA, Alagbonsi IA, Abdulkadir HO, Idowu FO. Low dose of melatonin ameliorates cryptorchidism-induced spermatotoxicity in rats. J Anat Soc India. 2017;66(1):67–71.CrossRef
25.
go back to reference Da Porto C, Decorti D, Tubaro F. Fatty acid composition and oxidation stability of hemp (Cannabis sativa L.) seed oil extracted by supercritical carbon dioxide. Ind Crop Prod. 2012;36(1):401–4.CrossRef Da Porto C, Decorti D, Tubaro F. Fatty acid composition and oxidation stability of hemp (Cannabis sativa L.) seed oil extracted by supercritical carbon dioxide. Ind Crop Prod. 2012;36(1):401–4.CrossRef
26.
go back to reference Deferne JL, Pate DW. Hemp seed oil: a source of valuable essential fatty acids. J Int Hemp Assoc. 1996;3(1):4–7. Deferne JL, Pate DW. Hemp seed oil: a source of valuable essential fatty acids. J Int Hemp Assoc. 1996;3(1):4–7.
27.
go back to reference Rausch P. Verwendung von hanfsameno in der kosmetik. In: Bioresource hemp. 2nd ed. Cologne: Nova-Institute; 1995. p. 556–61. Rausch P. Verwendung von hanfsameno in der kosmetik. In: Bioresource hemp. 2nd ed. Cologne: Nova-Institute; 1995. p. 556–61.
28.
go back to reference Westerman D, Santos R, Bosley J, Rogers J, Al-Duri B. Extraction of Amaranth seed oil by supercritical carbon dioxide. J Supercrit Fluids. 2006;37(1):38–52.CrossRef Westerman D, Santos R, Bosley J, Rogers J, Al-Duri B. Extraction of Amaranth seed oil by supercritical carbon dioxide. J Supercrit Fluids. 2006;37(1):38–52.CrossRef
29.
go back to reference Rubio-Rodriguez N, de Diego SM, Beltran S, Jaime I, Sanz MT, Rovira J. Supercritical fluid extraction of the omega-3 rich oil contained in hake (Merluccius capensis– Merluccius paradoxus) by-products: study of the influence of process parameters on the extraction yield and oil quality. J Supercrit Fluids 2008; 47(2): 215–226.CrossRef Rubio-Rodriguez N, de Diego SM, Beltran S, Jaime I, Sanz MT, Rovira J. Supercritical fluid extraction of the omega-3 rich oil contained in hake (Merluccius capensis– Merluccius paradoxus) by-products: study of the influence of process parameters on the extraction yield and oil quality. J Supercrit Fluids 2008; 47(2): 215–226.CrossRef
30.
go back to reference Al-Mutairi KA. Influence of soil physical and chemical variables on species composition and richness of plants in the arid region of Tabuk, Saudi Arabia. Ekologia (Bratislava). 2017;36(2):112–20.CrossRef Al-Mutairi KA. Influence of soil physical and chemical variables on species composition and richness of plants in the arid region of Tabuk, Saudi Arabia. Ekologia (Bratislava). 2017;36(2):112–20.CrossRef
31.
go back to reference Kirk ES, Graham JK, Squires EL. Increasing membrane cholesterol content benefits the motility of cooled equine semen. Anim Reprod Sci. 2001;68(3–4):317–8. Kirk ES, Graham JK, Squires EL. Increasing membrane cholesterol content benefits the motility of cooled equine semen. Anim Reprod Sci. 2001;68(3–4):317–8.
32.
go back to reference Schmid-Lausigk Y, Aurich C. Influences of a diet supplemented with oil and antioxidants on quality of equine semen after cooling and cryopreservation during winter. Theriogenology. 2014;81(7):966–73.PubMedCrossRef Schmid-Lausigk Y, Aurich C. Influences of a diet supplemented with oil and antioxidants on quality of equine semen after cooling and cryopreservation during winter. Theriogenology. 2014;81(7):966–73.PubMedCrossRef
33.
go back to reference Grady ST, Scott BD, Brinsko DW, Forrest DW, Sawyer JE, Cavinder CA. Dietary supplementation of 2 sources of omega-3 fatty acids and subsequent effects on fresh, cooled, and frozen seminal characteristics of stallions. J Equine Vet Sci. 2009;29(5):333–4.CrossRef Grady ST, Scott BD, Brinsko DW, Forrest DW, Sawyer JE, Cavinder CA. Dietary supplementation of 2 sources of omega-3 fatty acids and subsequent effects on fresh, cooled, and frozen seminal characteristics of stallions. J Equine Vet Sci. 2009;29(5):333–4.CrossRef
34.
go back to reference Rodrigues PG, de Moura RS, Rocha LGP, Bottino MP, Nichi M, Maculan R, Bertechini AG, Souza JC. Dietary polyunsaturated fatty acid supplementation improves the quality of stallion cryopreserved semen. J Equine Vet Sci. 2017;54:18–23.CrossRef Rodrigues PG, de Moura RS, Rocha LGP, Bottino MP, Nichi M, Maculan R, Bertechini AG, Souza JC. Dietary polyunsaturated fatty acid supplementation improves the quality of stallion cryopreserved semen. J Equine Vet Sci. 2017;54:18–23.CrossRef
35.
go back to reference Salman TM, Alagbonsi IA, Feyitimi AA. Role of reactive oxygen species-total anti-oxidant capacity status in Telfairia occidentalis leaves-associated spermatoprotective effect: a pointer to fatty acids benefit. J Basic Clin Physiol Pharmacol. 2018;29(4):347–58.PubMedCrossRef Salman TM, Alagbonsi IA, Feyitimi AA. Role of reactive oxygen species-total anti-oxidant capacity status in Telfairia occidentalis leaves-associated spermatoprotective effect: a pointer to fatty acids benefit. J Basic Clin Physiol Pharmacol. 2018;29(4):347–58.PubMedCrossRef
36.
go back to reference Battista N, Rapino C, Di Tommaso M, Bari M, Pasquariello N, Maccarrone M. Regulation of male fertility by the endocannabinoid system. Mol Cell Endocrinol. 2008;286(1–2):S17–23.PubMedCrossRef Battista N, Rapino C, Di Tommaso M, Bari M, Pasquariello N, Maccarrone M. Regulation of male fertility by the endocannabinoid system. Mol Cell Endocrinol. 2008;286(1–2):S17–23.PubMedCrossRef
37.
go back to reference Francavilla F, Battista N, Barbonetti A, Vassallo MR, Rapino C, Antonangelo C, Catanzaro G, Barboni B, Maccarrone M. Characterization of the endocannabinoid system in human spermatozoa and involvement of transient receptor potential vanilloid 1 receptor in their fertilizing ability. Endocrinology. 2009;150(10):4692–700.PubMedCrossRef Francavilla F, Battista N, Barbonetti A, Vassallo MR, Rapino C, Antonangelo C, Catanzaro G, Barboni B, Maccarrone M. Characterization of the endocannabinoid system in human spermatozoa and involvement of transient receptor potential vanilloid 1 receptor in their fertilizing ability. Endocrinology. 2009;150(10):4692–700.PubMedCrossRef
38.
go back to reference Agirregoitia E, Carracedo A, Subiran N, Valdivia A, Agirregoitia N, Peralta L, Velasco G, Irazusta J. The CB(2) cannabinoid receptor regulates human sperm cell motility. Fertil Steril. 2010;93(5):1378–87.PubMedCrossRef Agirregoitia E, Carracedo A, Subiran N, Valdivia A, Agirregoitia N, Peralta L, Velasco G, Irazusta J. The CB(2) cannabinoid receptor regulates human sperm cell motility. Fertil Steril. 2010;93(5):1378–87.PubMedCrossRef
39.
go back to reference Ramadan MF, Moersel JT. Screening of the antiradical action of vegetable oils. J Food Comp Anal. 2006;19(8):838–42.CrossRef Ramadan MF, Moersel JT. Screening of the antiradical action of vegetable oils. J Food Comp Anal. 2006;19(8):838–42.CrossRef
Metadata
Title
Cannabinoid-deficient Benin republic hemp (Cannabis sativa L.) improves semen parameters by reducing prolactin and enhancing anti-oxidant status
Authors
Abdullateef Isiaka Alagbonsi
Luqman Aribidesi Olayaki
Halimat Amin Abdulrahim
Thomson Sijuade Adetona
Gbemileke Tobiloba Akinyemi
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2541-5

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