Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats
Introduction
Carica papaya L. (Caricaceae) is an important medicinal plant in Indian traditional medicine (Nadkarni, 1954, Chopra et al., 1958). The seeds of Carica papaya are reported to possess emmenagogue, abortifacient and antifertility properties (Chopra et al., 1958). The male antifertility property of the seeds of Carica papaya has been well documented (Das, 1980, Chinoy et al., 1985, Chinoy et al., 1995, Chinoy and Padman, 1996, Lohiya et al., 2001, Lohiya et al., 2005a). We have authenticated with series of experiments using different extraction procedures and with different animal models that the methanol sub-fraction (MSF) of the benzene chromatographic fraction of the chloroform extract of the seeds of Carica papaya possess 100% contraceptive efficacy, effected through inhibition of sperm motility in rats and langur monkeys and azoospermia in rabbits, without adverse systemic side effects and has been identified as a putative candidate for male contraception (Lohiya and Goyal, 1992, Lohiya et al., 1999a, Lohiya et al., 1999b, Lohiya et al., 2001, Lohiya et al., 2002, Lohiya et al., 2005b, Lohiya et al., 2008, Pathak et al., 2000, Manivannan et al., 2004). Initial attempts to identify the chemical composition of the MSF through IR, NMR−1 and MS revealed that the product is a homogeneous mixture of long chain fatty esters. The dose regimen of 50 mg/kg body weight/day has been standardized as one contraceptive dose (Lohiya et al., 2001, Lohiya et al., 2005a). Initial safety by single oral administration and daily oral administration up to 90-day period has already been reported (Lohiya et al., 2006). The present investigation is expected to provide necessary information towards clinical safety of MSF for long term use as a male contraceptive.
Section snippets
Test material
Fresh seeds of Carica papaya L. (Caricaceae) of honey dew variety were procured commercially, authenticated in the Department of Botany, University of Rajasthan, Jaipur (Voucher No. RUBL 16590), shade dried, powdered and refluxed with chloroform for 36 h at 58–60 °C. The resultant chloroform extract was subjected to silica gel column chromatography (60–120 mesh), eluted with benzene. The benzene chromatographic fraction of the chloroform extract was concentrated under reduced pressure and
Food and water intake
Food and water intake showed day to day fluctuations and the values were comparable to those of control animals (Data not shown).
Pre-terminal death
Pre-terminal deaths in four males, one each in Group I (Control) and Group III (100 mg) and two in Group IV (250 mg) and three females, two in Group IV (250 mg) and one in Group V (500 mg) were recorded. Autopsy of these animals showed no treatment related mortality, since gross morphology of all the vital organs appeared normal.
Body weight and organs weight
The final body weight of the control and
Discussion
The toxicological severity, through single dose administration and repeated dose administration up to 28 and 90 days up to 10 times the contraceptive doses has already been demonstrated in rats which revealed no treatment related adverse side effects (Lohiya et al., 2006). Limit test with single high dose at 2000 mg/kg body weight over the 14 days observation period also did not detect external toxic symptoms, mortality, morbidity, altered food and water intake, body and organs weight,
Acknowledgements
The investigation was supported by the Indian Council of Medical Research (ICMR), New Delhi. The authors are thankful to the Special Assistance Programme (Phase III)/Centre for Advanced Studies (CAS), University Grants Commission, New Delhi and the Head of the Department, for providing infrastructural facilities.
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2021, Scientific AfricanCitation Excerpt :Furthermore, the extracts induced a significant reduction of contractile response of epididymal tubules and sperm count and quality male rats [148,154]. It caused infertility by significantly inhibiting spermatogenesis in testes [154,155]. The PSEs also induced abortion, caused interference of a normal estrous cycle, and reduced progesterone levels in female rats considerably [148,157–160].
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2020, Nutritional Composition and Antioxidant Properties of Fruits and VegetablesCarica papaya seed extract slows human sperm
2019, Journal of EthnopharmacologyCitation Excerpt :Papaya seed extract has been used successfully as an alternative due to its antifungal activity, and specifically because of its ability to trigger reactive oxygen species (ROS) production and decrease mitochondrial membrane activity (Zhang and Chen, 2017). Several studies have investigated the mechanism of action of the contraceptive effects of C. papaya in various animals such as monkeys (Lohiya et al., 2002), rabbits (Lohiya et al., 2000b), dogs (Ortega-Pacheco et al., 2011) and rats (Goyal et al., 2010). Lohiya et al., 2002, 2008 have shown that oral administration of 50 mg/kg/day of the chloroform and benzene chromatographic C. papaya seed extract resulted in long-term, reversible azoospermia with no significant side effects in langur monkeys.
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2017, Biomedicine and PharmacotherapyCitation Excerpt :It is used traditionally for its nutritional and medicinal properties [17]. Literature shows the medicinal use of papaya tree (fruit, seed and leaf) in the treatment of cardiovascular diseases, dengue fever, digestion disorders, inflammatory disorders, wound healing, malaria, hypoglycaemia, hyperlipidaemia, bacterial and fungal diseases, and as a male contraceptive [18–28]. Numerous case studies have also demonstrated its protective effects against the cancers of colorectal [29], prostate [30], cervical [31], breast [32], and gall bladder [33].
Evaluation of anxiolytic and sedative effects of 80% ethanolic Carica papaya L. (Caricaceae) pulp extract in mice
2013, Journal of EthnopharmacologyCitation Excerpt :Since last three decades, data are accumulating to systemically evaluate the traditional claims of its application in different cases. Its male contraceptive effect has been widely evaluated and study of the alkaloid extract of Carica papaya seeds prevented ovum fertilization, reduced sperm cell counts, sperm cell degeneration and induced testicular cell lesion, changes that induce reversible male infertility and a potential for a pharmaceutical male contraceptive (Lohiya et al., 2000; Goyal et al., 2010). While in female, unripe or semi-ripe papaya that contains high concentration of latex produces marked uterine contraction and may be unsafe during pregnancy as evidenced in animal studies (Anuar et al., 2008; Abdulazeez et al., 2009).