Abstract
Background:
Diabetic mellitus is a major global health problem characterized by chronic hyperglycemia-induced oxidative stress and impaired antioxidant defense mechanisms. Bitter melon (M.charantia), a plant rich in antioxidant phytochemicals, has been proposed as an antihyperglycemic agent.

Aim:
This study aimed to investigate the effects of bitter melon extract on serum 8-Iso-PGF₂, 8-OHdG, and antioxidant enzyme levels, as well as pancreatic histopathological and the expression of pancreatic superoxide dismutase (SOD) and insulin in STZ-induced diabetic rats.

Methods:
A total of 25 male Sprague–Dawley rats were randomly assigned to five groups: a normal control group (P0), an untreated diabetic group (P1), and three diabetic groups (P2–P4). Oral administration of bitter melon extract at doses of 25, 50, or 100 mg/kg body weight was performed for 21 days. At the end of the treatment period, serum and pancreatic tissues were collected to evaluate the levels of 8-isoprostaglandin (8-Iso-PGF₂) and 8-hydroxy-2-deoxyguanosine (8-OHdG), antioxidant enzyme levels (SOD, CAT, and GPx), pancreatic histopathological changes, and SOD and insulin immunohistochemical expression.

Results:
The results showed that treatment ethanolic extract of bitter melon (M. charantia) in diabetic rats was able to reduce blood glucose levels, exert protective effects against pancreatic β-cell damage and preservation of the pancreatic islets of Langerhans area, and decrease antioxidant enzyme levels, as well as serum 8-Iso-PGF₂ and 8-OHdG levels. However, these parameters had not fully returned to normal control levels. In addition, increased expression intensity of SOD and insulin was observed in the pancreatic islets of Langerhans.

Conclusion:
Treatment with ethanolic extract of M.charantia in STZ-induced diabetic rats showed potential antihyperglycemic effects, protection against pancreatic β-cell damage, and the ability to reduce 8-OHdG, 8-Iso-PGF2α, and serum antioxidant enzyme levels.

Key words: Antioxidant enzyme; Bitter melon; Diabetic; Hyperglycemia; Oxidative stress.