Cyclophosphamide: Potential Hepatorenal Toxicity and the Possible Therapeutic Role of Mesenchymal Stem Cell-Derived Exosomes in Wistar Rats.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

This study aimed to examine therapeutic impact of exosomes derived from adipose tissue- mesenchymal stem cells (AD-MSCs-Exos) on a rat model of hepatorenal toxicity. 32 Wistar male rats were grouped into 4 groups: Control group, rats received intraperitoneally (i.p.) phosphate buffered saline (PBS). Cyclophosphamide (CTX) group, rats injected i.p. with a single dose of CTX (50 mg/kg) followed by rotating doses of 8 mg/kg of CTX daily for 2 weeks. CTX + AD-MSCs group, rats infused with (1 × 10 6 AD-MSCs cells/rat) dissolved in PBS intravenously (i.v.) day after day for 1 week starting from second day of CTX last dose. CTX + AD-MSCs-Exos group, rats injected with 100 μg of Exos derived from AD-MSCs in 1 ml PBS by i.v. injection for 1 week starting from second day of CTX last dose. 5 weeks following initial CTX dose, blood, liver, and kidneys extracted. Serum alanine transaminase (ALT), aspartate transaminase (AST), creatinine and urea levels; hepatic malate dehydrogenase (MDH) and glutamate dehydrogenase (GLDH); renal kidney injury molecule-1 (KIM-1) and clusterin measured. Tumor necrosis factor alpha (TNF-α) and malonialdehyde (MDA) were estimated in hepatic and renal tissues. Furthermore, nuclear factor kappa B/toll like receptor-4 (NF-κB/TLR-4), nuclear factor erythroid 2- related factor 2/heme oxygenase-1 (Nrf-2/HO-1) and BCL-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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