title: Treatment with Azadirachta indica in diabetic pregnant rats: negative effects on maternal outcome.
abstract: BACKGROUND
  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).
  
  
  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 1.0mg/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 (1.0mg/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.
  
  
  CONCLUSIONS
  Both neem seed oil and azadirachtin impaired intrauterine development and altered antioxidant/oxidative status during pregnancy.
authors.affiliation: 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. brunadallaqua@gmail.com
authors.forename: Bruna
authors.initials: B
authors.lastname: Dallaqua
authors.forename: Felipe Hiroshi
authors.initials: FH
authors.lastname: Saito
authors.forename: Tiago
authors.initials: T
authors.lastname: Rodrigues
authors.forename: Iracema Mattos Paranhos
authors.initials: IM
authors.lastname: Calderon
authors.forename: Marilza Vieira Cunha
authors.initials: MV
authors.lastname: Rudge
authors.forename: Emilio
authors.initials: E
authors.lastname: Herrera
authors.forename: Débora Cristina
authors.initials: DC
authors.lastname: Damasceno
mesh_terms: D000818:Animals; D031601:Azadirachta; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005327:Fetal Resorption; D005951:Glucose Tolerance Test; D005989:Glycerides / Q000009:adverse effects*; D036701:Limonins / Q000009:adverse effects*; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D011247:Pregnancy; D011256:Pregnancy Outcome; D011254:Pregnancy in Diabetics / Q000378:metabolism; D051381:Rats; D012639:Seeds; D013729:Terpenes / Q000009:adverse effects*
chemical_list: D005989:Glycerides; D036701:Limonins; D013729:Terpenes; C002443:neem oil; D008315:Malondialdehyde; C010329:azadirachtin