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Cyclophosphamide (CTX) group, rats injected i.p. with a single dose of CTX (50\u2009mg\/kg) followed by rotating doses of 8\u2009mg\/kg of CTX daily for 2 weeks. CTX\u2009+\u2009AD\u2010MSCs group, rats infused with (1\u2009\u00d7\u200910\n                    <jats:sup>6<\/jats:sup>\n                    AD\u2010MSCs cells\/rat) dissolved in PBS intravenously (i.v.) day after day for 1 week starting from second day of CTX last dose. CTX\u2009+\u2009AD\u2010MSCs\u2010Exos group, rats injected with 100\u2009\u03bcg of Exos derived from AD\u2010MSCs in 1\u2009ml 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\u20101 (KIM\u20101) and clusterin measured. Tumor necrosis factor alpha (TNF\u2010\u03b1) and malonialdehyde (MDA) were estimated in hepatic and renal tissues. Furthermore, nuclear factor kappa B\/toll like receptor\u20104 (NF\u2010\u03baB\/TLR\u20104), nuclear factor erythroid 2\u2010 related factor 2\/heme oxygenase\u20101 (Nrf\u20102\/HO\u20101) and BCL\u20102\u2010associated X protein\/B\u2010cell lymphoma 2 (Bax\/Bcl\u20102) signaling pathways were analyzed by qRT\u2010PCR. Immunohistochemical staining for cyclooxygenase\u20102 \u201cCOX\u20102\u201d and inducible nitric oxide synthase \u201ciNOS\u201d performed in hepatic and renal tissues. Finally, histopathological investigation of both liver and kidney tissue carried out. Treatment with MSCs and their derived exosomes markedly improved antioxidant and anti\u2010inflammatory markers while reducing apoptotic gene expression compared to CTX group. Specifically, in liver tissues; Bax expression decreased 2.6\u2010fold and 3.3\u2010fold, while Bcl\u20102 increased 3.1\u2010fold and 1.8\u2010fold in AD\u2010MSCs\u2010 and AD\u2010MSCs\u2010Exos groups, respectively. Similarly, NF\u2010\u03baB was reduced 1.5\u2010fold and 2.8\u2010fold; Nrf2 and HO\u20101 were upregulated by approximately 7.4\u2010 and 5.2\u2010fold (AD\u2010MSCs) and 7.4\u2010 and 6.2\u2010fold (AD\u2010MSCs Exos), respectively compared to CTX group. In kidney tissues, Compared to CTX group, Bax expression decreased by approximately 1.5\u2010fold and 3.6\u2010fold, whereas Bcl\u20102 increased 3.0\u2010fold and 4.4\u2010fold in AD\u2010MSCs\u2010 and AD\u2010MSCs Exos groups, respectively. NF\u2010\u03baB and TLR\u20104 both were\u00a0downregulated by ~2.6 (AD\u2010MSCs) and 7.9, 2.1\u2010fold (AD\u2010MSCs Exos), while Nrf2 and HO\u20101 were upregulated by 12.1 and 2.2\u2010 fold (AD\u2010MSCs); 12.8\u2010 and 3.0\u2010fold (AD\u2010MSCs Exos), respectively. These findings confirm that both treatments mitigate CTX induced hepatorenal injury through modulation of apoptosis, inflammation, and oxidative stress pathways, with exosomes exhibiting slightly superior therapeutics efficacy. Also, immunological and histopathological investigation verified curative effect of MSCs\u2010Exos against CTX\u2010induced hepatorenal toxicity. These findings highlight that both AD\u2010MSCs and their exosomes confer significant therapeutic effect against CTX\u2010induced hepatorenal toxicity through modulation of apoptosis, inflammation, and oxidative stress pathways. Importantly, AD\u2010MSCs\u2010Exos demonstrated superior therapeutic efficacy compared to AD\u2010MSCs in restoring antioxidant defenses and attenuating inflammatory and apoptotic responses in both liver and kidney tissues.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70705","type":"journal-article","created":{"date-parts":[[2026,1,26]],"date-time":"2026-01-26T13:39:27Z","timestamp":1769434767000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Cyclophosphamide: Potential Hepatorenal Toxicity and the Possible Therapeutic Role of Mesenchymal Stem Cell\u2010Derived Exosomes in\n                    <i>Wistar<\/i>\n                    Rats"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0517-6470","authenticated-orcid":false,"given":"Ahmed N.","family":"Abdallah","sequence":"first","affiliation":[{"name":"Hormones Department, Medical Research and Clinical Studies Institute 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