Abstract
Background:
Cisplatin is a widely used chemotherapeutic agent in both human and veterinary medicine, particularly in canine osteosarcoma protocols. However, its use still carries the risk of dose-dependent toxicity, one of which is cisplatin-induced vascular toxicity, caused by oxidative stress and endothelial dysfunction. This toxicity can be exacerbated by pre-existing metabolic diseases which have vascular complications, such as diabetes mellitus (DM). Moringa oleifera Lam., a widely studied herbal remedy as an adjuvant therapy, is known to possess high antioxidant and anti-inflammatory properties. However, its vasculoprotective potential, especially in clinically relevant DM-cisplatin model, remains unexplored.

Aim:
This study examined the vasculoprotective effects of Moringa oleifera Lam. leaf extract (MOLE) in reducing cisplatin-induced vascular toxicity in DM rat models, specifically focusing on the mechanisms of oxidative stress and endothelial activation biomarkers.

Methods:
Thirty-five male Sprague Dawley rats were randomly divided into seven groups (n=5 each). Type 2 DM (T2DM) was induced using nicotinamide-streptozotocin, followed by cisplatin (8 mg/kg BW) administration. Treatment groups received MOLE at 350, 700, 1050 mg/kg BW for 14 days, while positive controls received erythropoietin (EPO). Serum malondialdehyde (MDA), E-selectin, NF-κB, and C-reactive protein (CRP) levels were quantified using ELISA, and systolic blood pressure (SBP) was measured.

Results:
Cisplatin-treated diabetic rats showed significant elevations in MDA, E-selectin, NF-κB, CRP, and SBP compared to controls (p<0.001). MOLE treatment produced dose-dependent improvements, with the highest dose (1050 mg/kg BW) reducing MDA by 83.8%, E-selectin by 83.0%, NF-κB by 90.4%, and CRP by 69.0%. SBP decreased from 213.0±5.05 to 97.8±3.34 mmHg (p<0.001). Strong correlations were observed between SBP and all biomarkers (r>0.96, p<0.001).

Conclusion:
MOLE reduced cisplatin-induced vascular toxicity in a diabetic rat model through antioxidant and anti-inflammatory mechanisms. These preclinical findings, obtained in a rodent model of T2DM, are hypothesis-generating and warrant further investigation in species-specific models, including canine studies, before any translational application in veterinary oncology is considered.

Key words: Cisplatin-induced toxicity; Diabetes mellitus; Endothelial dysfunction; Moringa oleifera Lam.; Oxidative stress.