title: Acute toxicity and gastroprotection studies with a newly synthesized steroid.
abstract: BACKGROUND
  Synthetic steroids, such as 9α-bromobeclomethasonedipropionate, have shown gastroprotective activity. For example, the potent glucocorticoid steroid, beclomethasone dipropionate, has been used for treatment of bowel ulcerations. The purpose of the present study was to evaluate the effect of a synthetic steroid, (20S)-22-acetoxymethyl-6β-methoxy-3α,5-dihydro-3'H-cyclopropa[3α,5]-5α-pregnane (AMDCP), on ethanol-induced gastric mucosa injuries in rats.
  
  
  RESULTS
  Rats were divided into 8 groups. The negative control and ethanol control groups were administered Tween 20 (10%v/v) orally. The reference control group, 20 mg/kg omeprazole (10% Tween 20, 5 mL/kg), was administrated orally. The experimental groups received 1, 5, 10, 15 or 20 mg/kg of the AMDCP compound (10% Tween 20, 5 mL/kg). After 60 min, Tween 20 and absolute ethanol was given orally (5 mL/kg) to the negative control group and to the rest of the groups, and the rats were sacrificed an hour later. The acidity of gastric content, gastric wall mucus and areas of mucosal lesions were assessed. In addition, histology and immunohistochemistry of the gastric wall were assessed. Prostaglandin E2 (PGE2) and malondialdehyde (MDA) content were also measured. The ethanol control group exhibited severe mucosal lesion compared with the experimental groups with fewer mucosal lesions along with a reduction of edema and leukocyte infiltration. Immunohistochemical staining of Hsp70 and Bax proteins showed over-expression and under-expression, respectively, in the experimental groups. The experimental groups also exhibited high levels of PGE2 as well as a reduced amount of MDA. AMDCP decreased the acidity and lipid peroxidation and increased the levels of antioxidant enzymes.
  
  
  CONCLUSIONS
  The current investigation evaluated the gastroprotective effects of AMDCP on ethanol-induced gastric mucosal lesions in rats. This study also suggests that AMDCP might be useful as a gastroprotective agent.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Kamal A
authors.initials: KA
authors.lastname: Ketuly
authors.forename: A Hamid A
authors.initials: AH
authors.lastname: Hadi
authors.forename: Shahram
authors.initials: S
authors.lastname: Golbabapour
authors.forename: Maryam
authors.initials: M
authors.lastname: Hajrezaie
authors.forename: Pouya
authors.initials: P
authors.lastname: Hassandarvish
authors.forename: Hapipah Mohd
authors.initials: HM
authors.lastname: Ali
authors.forename: Nazia
authors.initials: N
authors.lastname: Abdul Majid
authors.forename: Mahmood A
authors.initials: MA
authors.lastname: Abdulla
mesh_terms: D000818:Animals; D000431:Ethanol / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects*; D007150:Immunohistochemistry; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: D013256:Steroids; D000431:Ethanol