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Treatment with Azadirachta indica in diabetic pregnant rats: Negative effects on maternal outcome
Authors:Bruna Dallaqua,Felipe Hiroshi Saito,Tiago Rodrigues,Iracema Mattos Paranhos Calderon,Marilza Vieira Cunha Rudge,Emilio Herrera,Dé  bora Cristina Damasceno
Affiliation:1. Laboratory of Experimental Research on Gynecology and Obstetrics, Postgraduation Program in Gynecology, Obstetrics and Mastology, Botucatu Medical School, Universidade Estadual Paulista—UNESP, São Paulo State, Brazil;2. ABC Federal University (UFABC), Center of Natural and Human Sciences (CCNH), São Paulo State, Brazil;3. Faculties of Pharmacy and Medicine, Universidad San Pablo CEU, Boadilla del Monte, Madrid, Spain
Abstract:

Ethnopharmacological relevance

The role of Azadirachta indica (neem) against Chagas disease and its antibiotic and antidiabetic action have been demonstrated in non-pregnant animals. However, the effects of neem on lipid metabolism and oxidative stress during pregnancy remain to be investigated. The objective of this study was to evaluate the effects of Azadirachta indica (neem) on maternal reproductive performance and biochemical parameters in non-diabetic and streptozotocin-induced mild diabetic rats (MD).

Materials and methods

Pregnant rats were randomly distributed into six experimental groups: ND=non-treated non-diabetic (n=13); NDOil=non-diabetic treated with 1.2 mL/day neem seed oil (n=12); NDPA=non-diabetic treated with 1.0 mg/mL/day azadirachtin (n=12); D=non-treated diabetic (n=13); DOil: diabetic treated with neem seed oil (n=12), and DPA=diabetic treated with azadirachtin, n=13. Treatment with either neem oil (1.2 mL/day) or azadirachtin (1.0 mg/mL/day) was orally administered throughout pregnancy. Glucose test tolerance (GTT) was performed at day 17 of pregnancy and used as an inclusion criterion. At term pregnancy, maternal reproductive outcomes, lipid profile and oxidative stress status were assessed.

Results

Treatment with neem oil and azadirachtin during pregnancy (1) had no hypoglycemic and anti-hyperglycemic effects on non-diabetic and diabetic rats, respectively; (2) affected OGTT glycemic levels in diabetic rats; (3) increased the proportion of fetuses classified as small for pregnancy age (SPA) in all groups; and (4) did not interfere with the lipid profile in non-diabetic dams. Neem oil reduced the rate of total cholesterol and NEFA in diabetic animals. Both neem oil and azadirachtin increased lipoperoxidation, characterized by increased MDA levels in non-diabetic rats.

Conclusion

Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.
Keywords:APA, appropriate for pregnancy age   AUC, area under the curve   CHO, total cholesterol   D, diabetic non-treated   DM, diabetes mellitus   DM1, type 1 diabetes mellitus   DOil, diabetic treated with seed oil neem   DPA, diabetic treated with azadirachtin   GSH-Px, glutathione peroxidase   HDL, high-density lipoprotein   HSL, hormone-sensitive lipase   IL-10, Interleukin 10   LPA, Large for pregnancy age   ND, non-diabetic non- treated (ND, n=13)   NDOil, non-diabetic treated with seed oil neem   NDPA, non-diabetic treated with azadirachtin   NEFA, non-esterified fatty acids   OGTT, oral glucose test tolerance   ROS, reactive oxygen species   SC, subcutaneously   SD, standard deviation   SH, thiol groups   SOD, superoxide dismutase   SPA, small for pregnancy age   STZ, streptozotocin   TBARS, thiobarbituric acid reactive substances   TG, triglycerides.
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