What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin-induced liver injury (n=35). Intervention: Alamandine vs. Doxorubicin alone. Primary outcome: Serum alanine transaminase (ALT) levels (p=<0.05).

May 3, 2025Open Access

Protective effects of Alamandine against doxorubicin-induced liver injury in rats

Q: What are the key findings of this study?

Alamandine treatment significantly mitigated doxorubicin-induced hepatotoxicity in rats, reducing serum ALT levels from 286 U/L to 109.14 U/L (p<0.05) and restoring hepatic antioxidant capacity.

Q: What does this research mean for the field?

Alamandine effectively mitigates doxorubicin-induced hepatotoxicity in rats through antioxidant and anti-inflammatory mechanisms. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

AHAva Soltani HekmatFasa University of Medical Sciences MHMaryam HekmatShiraz University of Medical Sciences SRSepehr RamezanipourFasa University of Medical Sciences

Key Result

Alamandine treatment significantly mitigated doxorubicin-induced hepatotoxicity in rats, reducing serum ALT levels from 286 U/L to 109.14 U/L (p<0.05) and restoring hepatic antioxidant capacity.

Structured PICO

Does alamandine prevent doxorubicin-induced liver injury in male Wistar rats?

Population

35 male Wistar rats weighing 180-220g were randomized to evaluate the protective effects of alamandine against doxorubicin-induced liver injury over 42 days.

Intervention

Alamandine (50 µg/kg/day) administered continuously via mini-osmotic pumps for 42 days

Comparator

Doxorubicin alone (implied)

Outcome

Liver toxicity assessed through biochemical measurements of oxidative stress markers, inflammatory cytokines, liver enzymes, and histological examinationsurrogate

Alamandine effectively mitigates doxorubicin-induced hepatotoxicity in a rat model through antioxidant and anti-inflammatory mechanisms.

Main Result

Absolute Event Rate: 109.14% vs 286%

p-value: p=<0.05

Limitations

The potential influence of alamandine on phase I or II enzymes involved in doxorubicin metabolism was not assessed.
The potential impact of alamandine on the anticancer efficacy of doxorubicin was not evaluated in tumor-bearing models.

Abstract

BACKGROUND: Doxorubicin (DOX), a common chemotherapeutic agent, is often associated with dose-limiting hepatotoxicity. Alamandine, a peptide of the renin-angiotensin system, has shown antioxidant and anti-inflammatory properties that may counteract these adverse effects. OBJECTIVE: This study investigated the protective effects of alamandine on DOX-induced liver injury in rats. METHODS: Male Wistar rats received DOX (3.75 mg/kg intraperitoneally) on days 14, 21, 28, and 35, reaching a cumulative dose of 15 mg/kg. Alamandine (50 µg/kg/day) was administered continuously via mini-osmotic pumps for 42 days. Liver toxicity was assessed through biochemical measurements of oxidative stress markers, inflammatory cytokines, and liver enzymes, as well as histological examination. RESULTS: DOX administration significantly increased serum alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and malondialdehyde (MDA) levels while reducing superoxide dismutase (SOD) and catalase (CAT) activity. Histological analysis revealed hydropic degeneration and hepatocyte necrosis. Alamandine co-treatment restored SOD and CAT activity, reduced MDA and inflammatory markers, and normalized liver enzyme levels, indicating significant hepatoprotection. Furthermore, treatment with alamandine reduced the expression of pro-inflammatory cytokines IL-6, IL-1, and NF-κB induced by DOX, while p53 expression remained unchanged. CONCLUSION: Alamandine effectively mitigates DOX-induced hepatotoxicity, demonstrating its therapeutic potential as an adjunctive agent in chemotherapy through its antioxidant and anti-inflammatory mechanisms.

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