Cyclophosphamide (CP) is a chemotherapeutic agent which is extensively used in the treatment of multiple neoplastic and nonneoplastic diseases like breast cancer, lymphomas, systemic lupus erythematosus, and multiple sclerosis. Dose‐limiting side effects, mainly nephrotoxicity is a major problem hindering its use in the clinical practice. CP induces nephrogenic syndrome of inappropriate antidiuresis mostly via the activation of arginine vasopressin V 2 receptors. Moreover, CP produces reactive metabolites which is responsible for augmentation of lipid peroxidation and oxidative stress. Tolvaptan (TOL) is a selective vasopressin V 2 receptor antagonist used in the treatment of clinically significant hyponatremia, volume overload in heart failure, and liver cirrhosis with edema. The present study aimed to investigate the potential protective effect of TOL in CP‐induced nephrotoxicity. Twenty‐four adult male albino rats were randomly divided into four groups: the control group, TOL group that treated daily with tolvaptan (10 mg/kg/d, orally), CP group where CP was administered intraperitoneally 75 mg/kg on days 3, 4, 5, 19, 20, and 21 of study, and the CP + TOL group where animals were treated with TOL daily with (10 mg/kg/d, orally) for 22 days with concomitant administration of CP as described before. Coadministration of TOL with CP induces significant improvement in the level of urine volume, serum Na+, serum osmolarity, urinary creatinine, and free water clearance in addition to significant reduction of body weight, serum creatinine, urea, serum K+, blood pressure, urine osmolarity, and the fractional excretion of sodium as compared to CP‐treated group. In addition, coadministration of TOL significantly reduced MDA, the marker of lipid peroxidation, and different pro‐inflammatory cytokines. Histopathological changes showed improvement in the signs of nephrotoxicity with the coadministration of TOL. Also, co‐treatment with TOL significantly decreased the level of markers of apoptosis as caspase‐3 and Bax with increased expression of antiapoptotic Bcl‐2 in renal tissue as compared to CP‐treated group.

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The stem cells with their distinct ability of self-renewal and differentiation are considered an innovation in wound healing. However, there is lack of studies comparing the differential effect of the type and administration route of stem cells in the wound healing context. Thus, the current study has been designed to elucidate the effect of two of the most important stem cell types-the bone marrow-derived and adipose-derived stem cells in full thickness wound healing-and to evaluate, in this optimized wound model, the effectiveness of intradermal versus intravenous routes using H&E, Masson's trichrome, and PKH26-stained sections. It also evaluated the immunohistochemical expression of the stem cell-related surface markers-Ki67, CD71, CD146, CD90, and CD163-and also assessed the level of TNFα and gene expression of NF-κB as two important inflammatory markers. The study revealed that the adipose stem cell groups have shown statistically significant improvement in inflammation, granulation tissue re-organization, and collagen deposition relative to their bone marrow-treated counterparts. The intradermally treated adipose stem cell group, in particular, has demonstrated the most supreme features regarding the expression of the proliferation-related surface markers Ki67 and CD71 as well as in the expression of CD90 in keratinocytes and hair follicle dermal sheaths. The same group has shown the lowest level of TNFα and the best outcome in the parameters of neo-epidermal thickness, granulation tissue re-organization, and pattern of collagen deposition. The systemically treated wounds have displayed superior expression of CD146-positive endothelial cells and dermal fibroblasts as well as better expression of CD163+ macrophages.

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