Abstract
Background:
Levofloxacin (LEVO) is a commonly used, broad-spectrum fluoroquinolone antibiotic that is crucial for treating severe bacterial diseases. Despite its efficacy, emerging evidence links it to potential cardiotoxic effects, including rare but severe cases of myocardial injury. This underscores a critical need for effective adjunctive protective strategies. Nigella sativa (Black Seed) oil (NSO), a revered medicinal plant extract, possesses well-documented potent antioxidant, anti-inflammatory, and anti-apoptotic properties, primarily attributed to its major bioactive constituent, thymoquinone, offering a promising phytotherapeutic candidate for mitigating drug-induced organ toxicity.

Aim:
This study aimed to evaluate the cardioprotective efficacy of Nigella sativa oil against levofloxacin-induced myocardial damage in rats using histological examination and cardiac biomarker analysis.

Methods:
Forty adult male Wistar rats were allocated into four experimental groups (n = 10): Group I (Control) received the vehicle; Group II (LEVO) received 75 mg/kg/day levofloxacin orally; Group III (NSO) received 2 ml/kg/day Nigella sativa oil orally; and Group IV (LEVO + NSO) received the same doses of both LEVO and NSO. The treatment regimen lasted for 30 consecutive days. Following euthanasia, heart tissue and blood samples were collected for histological and biochemical analysis.

Results:
LEVO exhibited severe cardiotoxicity, marked by significant increases in all cardiac biomarkers compared with the control (Troponin I: 1.01 ± 0.03 vs. 0.04 ± 0.01 ng/mL, p < 0.001; CK-Total: 226.24 ± 4.70 vs. 55.42 ± 2.31 IU/L, p < 0.001; CK-MB: 90.07 ± 4.06 vs. 14.74 ± 0.91 IU/L, p < 0.001; LDH: 614.82 ± 34.60 vs. 250.28 ± 6.19 U/L, p < 0.001; and AST: 183.81 ± 6.37 vs. 120.27 ± 5.16 U/L, p < 0.001). Histopathologically, the LEVO-only group showed widespread Zenker's degeneration, coagulative necrosis, sarcoplasmic vacuolization, loss of myofibrillar architecture, vascular congestion with hemorrhage, and lymphocytic myocarditis with interstitial fibrosis. NSO co-treatment significantly reduced all biomarkers compared with LEVO alone (troponin I: 0.10 ± 0.01 vs. 1.01 ± 0.03 ng/mL, p < 0.001; CK-Total: 103.86 ± 3.18 vs. 226.24 ± 4.70 IU/L, p < 0.001; CK-MB: 30.46 ± 1.70 vs. 90.07 ± 4.06 IU/L, p < 0.001; LDH: 310.19 ± 11.80 vs. 614.82 ± 34.60 U/L, p < 0.001; and AST: 130.27 ± 3.18 vs. 183.81 ± 6.37 U/L, p < 0.01).However, while AST was fully restored to control levels (p > 0.05), troponin I, CK-Total, CK-MB, and LDH levels remained significantly elevated compared to control (p < 0.001 to p < 0.01), indicating partial rather than complete biochemical recovery for these markers. The LEVO + NSO group demonstrated well-preserved cardiac histoarchitecture with intact cardiomyocytes and only occasional mild lesions. These findings confirm the cardioprotective potential of NSO against levofloxacin-induced cardiotoxicity.

Conclusion:
Nigella sativa oil demonstrates significant cardioprotective efficacy against levofloxacin-induced toxicity, as it concurrently preserves normal cardiac histoarchitecture and improves key cardiac biomarkers. These findings suggest that NSO has potential as a promising natural adjuvant for safeguarding cardiac tissue during fluoroquinolone therapy; however, further studies incorporating cardiac function testing, electrocardiographic monitoring, and oxidative stress panels are warranted to more fully validate this effect.

Key words: Cardiotoxicity; Histopathology; Levofloxacin; Nigella sativa; Thymoquinone.