A Study on Preclinical Safety and Efficacy of MCP I Conjugated Gold Nanoparticles based oral contraceptive using Biomarkers of Reproductive Tissues and Blood Serum of Male Albino Wistar Rats
Abstract
Characterized MCP I fraction of Carica papaya seeds is being considered a potential contraceptive agent. Utilization of gold nanoparticles as a carrier molecule enhanced its targeted bioavailability, biocompatibility, in vitro stability against blood serum and pH gradient. In this study, preclinical safety and efficacy were assessed employing concerned biomarkers of blood serum and excised reproductive tissues for further approval of this nanoformulation. Experimental groups A, B & C were consists of vehicle control, orally treated with MCP I (50 mg/kg body wt./day) and MCP I conjugated gold nanoparticle (200µg/kg body wt./day) containing nine male albino Wistar rats in each. Three animals were sacrificed monthly interval during 90 days of investigation period. No significant differences were examined in markers of blood serum i.e., cholesterol, creatinine, lactate dehydrogenase, creatine kinase, bilrubin, urea, triglyceride, HDL and concentrations of testosterone, luteinizing hormone and follicle stimulating hormone except drastic reduction in SGOT (p< 0.001) and SGPT (p< 0.05; p< 0.01; p< 0.001) in group C. The glycogen, cholesterol and lactate dehydrogenase level in testicular tissues, sialic acid and fructose corresponded to epididymal and seminal vesicles, respectively, demonstrated insignificant changes. Significant diminution was recorded in the level of L-carnitine and α-glucosidase at 60 days in group B (p< 0.05) and 30 days in group C (p< 0.01; p< 0.001) of epididymal tissues. Prostatic acid phosphatase was increased (p< 0.05; p< 0.01) in group C. While antioxidant biomarkers in testicular tissues viz., lipid peroxidase, superoxide dismutase, reduced glutathione and catalase were revealed insignificant alteration. Thus, status of biomarkers indicate that synergistic effect of MCP I conjugated gold nanoparticle was found to be targeted, safe and effective for oral contraception in male albino rats at highly reduced dosage compared to pure MCP I treated animals which may open new avenues for clinical development.
Keywords:
Male contraceptive, Gold nanoparticle, Carica papaya seeds, MCP I fraction, Biomarkers of Tissue and Blood.DOI
https://doi.org/10.25004/IJPSDR.2022.140201References
Tinneke D, Thomas S, Maarten VR. Animal models in translational medicine: Validation and prediction. New Horiz. Transl. Med. 2014; 2:5-11.
Williams SA, Slavin DE, Wagner JA, Webster CJ. A cost-effectiveness approach to the qualification and acceptance of biomarkers. Nat. Rev. Drug Discov. 2006; 5:897-902.
Wagner JA. Strategic approach to fit-for-purpose biomarkers in drug development. Annu. Rev. Pharmacol. Toxicol. 2008; 48:631–651.
Kamp H, Strauss V, Wiemer J, Leibold E, Walk T, Mellert W, Looser R, Prokoudine A, Fabian E, Krennrich G, Herold M, van Ravenzwaay B. Reproducibility and robustness of metabolome analysis in rat plasma of 28-day repeated dose toxicity studies. Toxicol. Lett. 2012; 215:143–149.
Kamp H, Fabian E, Groeters S, Herold M, Krennrich G, Looser R, Mattes W, Mellert W, Prokoudine A, Ruiz-Noppinger P, Strauss V, Walk T, Wiemer J, van Ravenzwaay B. Application of in vivo metabolomics to preclinical/toxicological studies: case study on phenytoin-induced systemic toxicity. Bioanalysis 2012; 4:2291-2301
Strauss V, Mellert W, Wiemer J, Leibold E, Kamp H, Walk T, Looser R, Prokoudine A, Fabian E, Krennrich G, Herold M, van Ravenzwaay B. Increased toxicity when fibrates and statins are administered in combination - a metabolomics approach with rats. Toxicol. Lett. 2012; 211:187–200.
Newby LK, Rodriguez I, Finkle J, Becker RC, Hicks KA, Hausner E, Chesler R, Harper C, Targum S, Berridge BR, Lewis E, Walker DB, Dollery C, Turner JR, Krucoff MW. Troponin measurements during drug development—considerations for monitoring and management of potential cardiotoxicity: an educational collaboration among the Cardiac Safety Research Consortium, the Duke Clinical Research Institute, and the US Food and Drug Administration. Am. Heart J. 2011; 162:64–73.
Reagan WJ. Troponin as a biomarker of cardiac toxicity: past, present, and future. Toxicol. Pathol. 2010; 38:1134-1137.
Dieterle F, Perentes E, Cordier A, Roth DR, Verdes P, Grenet O, Pantano S, Moulin P, Wahl D, Mahl A, End P, Staedtler F, Legay F, Carl K, Laurie D, Chibout SD, Vonderscher J, Maurer G. Urinary clusterin, cystatin C, beta 2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat. Biotechnol. 2010; 28:463-469.
Engelmann G. Biomarkers in Focus: Alanine Aminotransferase. In: Patel V., Preedy V. (eds) Biomarkers in Liver Disease; Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht, 2017, pp. 267-280.
Parween S, Gupta PK, Chauhan VS. Induction of humoral immune response against PfMSP-119 and PvMSP-119 using gold nanoparticles along with alum. Vaccine. 2011; 29:2451–2460.
Mohammad I. Gold nanoparticle: An efficient carrier for MCP I of Carica papaya seeds extract as an innovative male contraceptive in albino rats. J. Drug Deliv. Sci. Technol. 2019; 52:942–956.
Zhang XD, Wu HY, Wu D, Wang YY, Chang JH, Zhai ZB, Meng AM, Liu PX, Zhang LA, Fan FY. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int. J. Nanomedicine, 2010; 5:771-781. doi: 10.2147/IJN.S8428
Montgomery R. Determination of glycogen. Arch. Biochem. Biophys. 1957; 67:378-386.
Bergmeyer HU. Methods of enzymatic analysis, Academic Press, New York and London, 1965.
King EJ, Wootton IDP. Microanalysis in medical biochemistry, Churchill, London, 1959, pp.42.
Cooper TG, Yeung CH, Nashan D, Neischlag E. Epididymal markers in human infertility. J. Androl. 1985; 9:91-101.
Wang ZP, Gu ZP, Cao L, Xu Y, You GD, Mao BY, Qian SZ. Effects of tripchlorolide on the epididymides and testes of rats. Asian J. Androl. 1999; 1:121-125.
Svennerholm L. Isolation and determination of neuraminic (sialic) acid by resorcinol reaction, In: Methods of Biochemical Analysis, Glick, D. (Ed.), Interscience, New Delhi, 1960, pp.214.
WHO, WHO laboratory manual for the examination of the human semen and sperm cervical mucus interaction, Cambridge University Press, New York, 1992.
Ohkawa H, Ohiahi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. 1979; 95:351-358.
Aebi H. Catalase in vitro. Methods Enzymol. 1984; 105:121-126.
Marklund S, Marklund G. Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur. J. Biochem. 1974; 47:469-474.
Beutler E, Duron O, Kelly BM. Improved method for the determination of blood glutathione. J. Lab. Clin. Med. 1963; 61:882-888.
Parveen A, Malashetty VB, Mantripragada B, Yalagatti MS, Abbaraju V, Deshpande R. Bio-functionalized gold nanoparticles: Benign effect in Sprague-Dawley rats by intravenous administration. Saudi J. Biol. Sci. 2017; 24:1925–1932.
Okada FK, Stumpp T, Miraglia S M. C arnitine r educes t esticular damage in rats treated with etoposide in the prepubertal phase. Cell Tissue Res. 2009; 337:269-80.
Ng CM, Blackman MR, Wang C, Swerdloff RS. The role of carnitine in the male reproductive system. Ann. NY. Acad. Sci. 2004; 1033:177-188.
Kalla NR, Kaur S, Ujwal N, Mehta U, Joos H, Frick J. Alpha-glucosidase activity in the rat epididymis under different physiological conditions. Int. J. Androl. 1997; 20:92-95.
Kalynovskyi VY, Pustovalov AS, Grodzyuk GY, Andriushyna NS, Dzerzhynsky MS. Effect of gold and silver nanoparticles on the morpho-functional state of the epididymis and prostate gland in rats. Vìsn. Dnìpropetr. Unìv. Ser. Bìol. Med. 2016; 7:106-111.
Afifi M, Almaghrabi OA, Kadasa N M. A meliorative e ffect o f z inc oxide nanoparticles on antioxidants and sperm characteristics in streptozotocin-induced diabetic rat testes. Biomed. Res. Int. 2015; 153573.
Ghosh S, Sengupta J, Datta P, Gomes A. Hematopoietic and antioxidant activities of gold nanoparticles synthesized by aqueous extract of Fenugreek (Trigonellafoenum-graecum) seed. Adv. Sci. Eng. Med. 2014; 6:546-552.
Liu L, He Y, Xiao Z, Tao W, Zhu J, Wang B, Liu Z, Wang M. Effects of selenium nanoparticles on reproductive performance of male sprague-dawley rats at supranutritional and nonlethal levels. Biol. Trace Elem. Res. 2017; 180:81-89.
Sulaiman FA, Akanji MA, Oloyede HOB, Sulaiman AA, Olatunde A, Joel EB, Adewale TH, Adeboye HA, Idris SO, Quadri AL, Oyegoke RA, Adeyemi OS. Oral Exposure to silver/gold nanoparticles: status of rat lipid profile, serum metabolites and tissue morphology. J. Med. Sci. 2015; 15:71-79.
Adeyemi OS, Whiteley CG. Interaction of nanoparticles with arginine kinase from Trypanosoma brucei: Kinetic and mechanistic evaluation. Int. J. Boil. Macromol. 2013; 62:450-456.
Adeyemi OS, Whiteley CG. Interaction of metal nanoparticles with recombinant arginine kinase from Trypanosoma brucei: Thermodynamic and spectrofluorimetric evaluation. Biochim. Biophys. Acta (BBA)-Gen. Subj. 2014; 1840:701-706.
Behnammorshedi M, Nazem H, Moghadam MS. The Effect of gold nanoparticle on luteinizing hormone, follicle stimulating hormone, testosterone and testis in male rat. Biomedical Research. 2015; 26:348-352.
Published
Abstract Display: 739 
PDF Downloads: 654 
