Effect of Cissus quadrangularis Linn on skeletal growth in the neonates of diabetic rats

Srinivasa Rao Sirasanagandla, K. Sreedhara Ranganath Pai, Kumar M. R. Bhat

Abstract


Background: Infants of the diabetic mother are known to have reduced bone mineral content and hypocalcemia. Earlier, it has been shown that petroleum ether extract of Cissus quadrangularis (PECQ) can enhance the fetal skeletal ossification in normal rats. The present study was designed to evaluate the effect of PECQ on skeletal growth in the neonatal rats of streptozotocin-induced diabetic rats.

Methods: After confirmation of diabetes, the diabetic and non-diabetic female Wistar rats were kept for mating with healthy male rats. After positive vaginal smear test, the pregnant rats were divided into three groups; the normal (non-diabetic) control (NC), diabetic control (DC), and diabetic+CQ (D+CQ) groups. The rats in the D+CQ group were given PECQ (500 mg/kg B.Wt), whereas animals in NC and DC groups were given 0.5% carboxy methyl cellulose, throughout the gestational period. Femur from the 1 week old neonatal rats from each group was collected randomly and subjected to histological analysis.

Results: Thickness of trabecular bone and periosteum was significantly reduced in the neonates of DC rats compared with the neonates of NC group. Pretreatment with PECQ significantly improved the thickness of trabecular bone and periosteum compared with neonatal rats of DC group. No significant differences were observed in the medullary cavity width of femur between the groups.

Conclusion: Data from the present study suggest that the PECQ can effectively attenuate the diabetes-induced reduction in the early skeletal growth. However, further research is warranted to evaluate the exact mechanism of action of phytochemical constituents of PECQ that can cross the placental barrier.


Keywords


Diabetic rats, Skeletal growth, Neonatal rats, Cissus quadrangularis, Trabecular bone

Full Text:

PDF

References


Goodman WG, Hori MT. Diminished bone formation in experimental diabetes. Relationship to osteoid maturation and mineralization. Diabetes. 1984;33(9):825-31.

McNair P, Christiansen C, Christensen MS, Madsbad S, Faber OK, Binder C, et al. Development of bone mineral loss in insulin-treated diabetes: a 1 1/2 years follow-up study in sixty patients. Eur J Clin Invest. 1981;11(1):55-9.

Marvin EL, Vincenza CB, Louis VA. Effects of diabetes mellitus in juvenile and adult onset diabetes. N Engl J Med. 1976;294(5):241-5.

Gunczler P, Lanes R, Paoli M, Martinis R, Villaroel O, Weisinger JR. Decreased bone mineral density and bone formation markers shortly after diagnosis of clinical type 1 diabetes mellitus. J Pediatr Endocrinol Metab. 2001;14(5):525-8.

Ersoy B, Göksen D, Darcan S, Mavi E, Oztürk C. Evaluation of bone mineral density in children with diabetes mellitus. Indian J Pediatr. 1999;66(3):375-9.

Tsang RC, Kleinman LI, Sutherland JM, Light IJ. Hypocalcemia in infants of diabetic mothers. Studies in calcium, phosphorus, and magnesium metabolism and parathormone responsiveness. J Pediatr. 1972;80(3):384-95.

Cruikshank DP, Pitkin RM, Varner MW, Williams GA, Hargis GK. Calcium metabolism in diabetic mother, fetus, and newborn infant. Am J Obstet Gynecol. 1983;145(8):1010-6.

Mimouni F, Steichen JJ, Tsang RC, Hertzberg V, Miodovnik M. Decreased bone mineral content in infants of diabetic mothers. Am J Perinatol. 1988;5(4):339-43.

Verrotti A, Chiarelli F, Capani F, Morgese G. Calcium metabolism in type 1 diabetes mellitus. Diabetes Nutr Metab. 1992;5:231-6.

Padmanabhan R, Al-Zuhair AGH. Effect of streptozotocin induced maternal diabetes on fetal skeletal development in the rat. Congenit Anom. 1988;29:151-63.

Braddock R, Simán CM, Hamilton K, Garland HO, Sibley CP. Gamma-linoleic acid and ascorbate improves skeletal ossification in offspring of diabetic rats. Pediatr Res. 2002;51(5):647-52.

Mughal MZ, Eelloo J, Roberts SA, Maresh M, Ward KA, Ashby R, et al. Body composition and bone status of children born to mothers with type 1 diabetes mellitus. Arch Dis Child. 2010;95(4):281-5.

Tein MS, Breen SA, Loveday BE, Devlin H, Balment RJ, Boyd RD, et al. Bone mineral density and composition in rat pregnancy: effects of streptozotocin-induced diabetes mellitus and insulin replacement. Exp Physiol. 1998;83(2):165-74.

Udupa KN, Chaturvedi GN, Tripathi SN. Advances in Research in Indian Medicine. Volume. 12. Varanasi, India: Banaras Hindu University; 1970: 165-96.

Stohs SJ, Ray SD. A review and evaluation of the efficacy and safety of Cissus quadrangularis extracts. Phytother Res 2013;27(8):1107-14.

Prasad GC, Udupa KN. Pathways and site of action of a phytogenic steroid from Cissus quadrangularis. J Res Indian Med. 1972;4:132.

Sen SP. Studies on the active constituents of Cissus quadrangularis wall. Curr Sci. 1966;35:317.

Rao MS, Potu BK, Swamy NVB, Kutty GN. Cissus quadrangularis plant extract enhances the development of cortical bone and trabeculae in the fetal femur. Pharmacologyonline. 2007;3(15):190-202.

Potu BK, Rao MS, Kutty NG, Bhat KM, Chamallamudi MR, Nayak SR. Petroleum ether extract of Cissus quadrangularis (LINN) stimulates the growth of fetal bone during intra uterine developmental period: a morphometric analysis. Clinics (Sao Paulo). 2008;63(6):815-20.

Regev RH, Dolfin T, Eliakim A, Arnon S, Bauer S, Nemet D, et al. Bone speed of sound in infants of mothers with gestational diabetes mellitus. J Pediatr Endocrinol Metab. 2004;17(8):1083-8.

Demarini S, Specker BL, Sierra RI, Miodovnik M, Tsang RC. Evidence of increased intrauterine bone resorption in term infants of mothers with insulin-dependent diabetes. J Pediatr. 1995;126(5):796-8.

Robertson SS, Dierker LJ. Fetal cyclic motor activity in diabetic pregnancies: sensitivity to maternal blood glucose. Dev Psychobiol. 2003;42(1):9-16.

Lindsay R, Hart DM, Aitken JM, MacDonald EB, Anderson JB, Clarke AC. Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet. 1976;1(7968):1038-41.

Wronski TJ, Cintrón M, Doherty AL, Dann LM. Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats. Endocrinology. 1988;123(2):681-6.

Takano-Yamamoto T, Rodan GA. Direct effects of 17 beta-estradiol on trabecular bone in ovariectomized rats. Proc Natl Acad Sci U S A. 1990;87(6):2172-6.

Gray TK, Flynn TC, Gray KM, Nabell LM. 17 beta-estradiol acts directly on the clonal osteoblastic cell line UMR106. Proc Natl Acad Sci U S A. 1987;84(17):6267-71.

Ernst M, Parker MG, Rodan GA. Functional estrogen receptors in osteoblastic cells demonstrated by transfection with a reporter gene containing an estrogen response element. Mol Endocrinol. 1991;5(11):1597-606.

Migliaccio S, Davis VL, Gibson MK, Gray TK, Korach KS. Estrogens modulate the responsiveness of osteoblast-like cells (ROS 17/2.8) stably transfected with estrogen receptor. Endocrinology. 1992;130(5):2617-24.

Komm BS, Terpening CM, Benz DJ, Graeme KA, Gallegos A, Korc M, et al. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science. 1988;241(4861):81-4.

Eriksen EF, Colvard DS, Berg NJ, Graham ML, Mann KG, Spelsberg TC, et al. Evidence of estrogen receptors in normal human osteoblast-like cells. Science. 1988;241(4861):84-6.

Migliaccio S, Newbold RR, Bullock BC, McLachlan JA, Korach KS. Developmental exposure to estrogens induces persistent changes in skeletal tissue. Endocrinology. 1992;130(3):1756-8.

Migliaccio S, Newbold RR, Bullock BC, Jefferson WJ, Sutton FG Jr, McLachlan JA, et al. Alterations of maternal estrogen levels during gestation affect the skeleton of female offspring. Endocrinology. 1996;137(5):2118-25.

Todaka E, Sakurai K, Fukata H, Miyagawa H, Uzuki M, Omori M, et al. Fetal exposure to phytoestrogens - The difference in phytoestrogen status between mother and fetus. Environ Res. 2005;99(2):195-203.

Mustafa AM, Malintan NT, Seelan S, Zhan Z, Mohamed Z, Hassan J, et al. Phytoestrogens levels determination in the cord blood from Malaysia rural and urban populations. Toxicol Appl Pharmacol. 2007;222(1):25-32.

Verhaeghe J, Van Herck E, Bouillon R. Umbilical cord osteocalcin in normal pregnancies and pregnancies complicated by fetal growth retardation or diabetes mellitus. Biol Neonate. 1995;68(6):377-83.

Potu BK, Bhat KM, Rao MS, Nampurath GK, Chamallamudi MR, Nayak SR, et al. Petroleum ether extract of Cissus quadrangularis (Linn.) enhances bone marrow mesenchymal stem cell proliferation and facilitates osteoblastogenesis. Clinics (Sao Paulo). 2009;64(10):993-8.

Gopalakrishnan V, Vignesh RC, Arunakaran J, Aruldhas MM, Srinivasan N. Effects of glucose and its modulation by insulin and estradiol on BMSC differentiation into osteoblastic lineages. Biochem Cell Biol. 2006;84(1):93-101.

Gopalakrishnan V, Arunakaran J, Aruldhas MM, Srinivasan N. Effects of streptozotocin-induced diabetes mellitus on some bone turnover markers in the vertebrae of ovary-intact and ovariectomized adult rats. Biochem Cell Biol. 2006;84(5):728-36.