Modulatory effects of concomitant quercetin/sitagliptin administration on the ovarian histological and biochemical alterations provoked by doxorubicin in a streptozotocin-induced diabetic rat model.

Limited literature was available on the effects of sitagliptin or quercetin treatments on doxorubicin induced ovarian dysfunction in diabetic animals. The study aim was test the efficacy and suggested mechanisms of quercetin/sitagliptin combined treatment on the doxorubicin-induced ovarian toxicity in rat model with streptozotocin-induced diabetes. Forty eight female Wistar rats were divided into six groups: 1) Control; 2) Streptozotocin induced diabetes; 3) Streptozotocin-induced diabetes + doxorubicin ovarian damage; 4) Streptozotocin-induced diabetes + doxorubicin ovarian damage with; 5) Streptozotocin-induced diabetes + doxorubicin ovarian damage with sitagliptin treatment and 6) Streptozotocin-induced diabetes + doxorubicin ovarian damage with concomitant quercetin/sitagliptin treatment. Biochemical tests for serum estrogen, progesterone, insulin, blood glucose, and ovarian levels of malondialdehyde, nitric oxide, and superoxide dismutase and qRT-PCR for NOBOX, FSHr, and iNOS genes were performed. Histological evaluation was done on ovary sections with hematoxylin and eosin and immunohistochemistry for 8-OHdG and iNOS followed by morphometric analysis. The streptozotocin-induced diabetic group showed varying degrees of follicle atresia and altered biochemical parameters, both were marked in the streptozotocin-induced diabetic + doxorubicin group. The mRNA of NOBOX, FSHr, and iNOS genes were disturbed with increased immunoexpression of iNOS and 8-OHdG. Quercetin and/or sitagliptin administration improved all altered histological and biochemical parameters and was more effective as a combined treatment. The study suggested equal efficacy of both quercetin and sitagliptin in mitigating the doxorubicin-induced ovarian toxicity in the streptozotocin diabetic rat model, and the combined therapy showed anti-inflammatory, anti-antioxidant, and anti-DNA damage mechanisms.

Structural and chemical role of mesenchymal stem cells and resveratrol in regulation of apoptotic -induced genes in Bisphenol-A induced uterine damage in adult female albino rats.

The probable beneficial effects of mesenchymal stem cells (MSCs) and resveratrol were assessed in an experimental model of Bisphenol-A (BPA)-evident uterine damage in rats. Thirty-five albino rats were involved and equally divided into five groups: Group I: negative control rats received usual diet, Group II: positive control rats received BPA by oral gavage for 15 days, Group III: BPA-treated rats received single oral gavage of resveratrol daily for two weeks, Group IV: BPA-treated rats received a single intravenous dose of MSCs and Group V: BPA-treated rats received combined treatment of resveratrol and MSCs. Oxidative stress markers, apoptosis-related genes, and gonadal hormones were assessed. Histological and immunohistochemical examination of uterine tissue was conducted for TGF-ß 1. Caspases-3, 8, and 9 (Casp3, Casp8, Casp9) genes were assessed in uterine tissues by quantitative real-time PCR. Results revealed that BPA induced significant changes in the endometrial tissue, inflammatory cell infiltration, focal blood extravasation, increase in collagen fibers, decrease in PAS staining, and increase in TGF-ß 1 immunoreactivity. BPA also induced a significant increase in oxidative stress markers; malondialdehyde (MDA), SOD, CAT, and apoptosis-related genes. BPA induced a significant change in blood levels of gonadal hormones; a significant increase in FSH and a significant decrease in estradiol (E2) and progesterone (P). Treatment with either resveratrol, MSCs, or a combination of them resulted in significant enhancement of histological findings, restoration of gonadal hormones to near-normal levels, and a significant decrease in oxidative stress markers and apoptosis genes. Combined treatment with resveratrol and MSCs demonstrated more significant therapeutic effects as regard to the studied parameters in association with rat groups treated with either MSCs or resveratrol separately.

Possible healing effects of Salvadora persica extract (MISWAK) and laser therapy in a rabbit model of a caustic-induced tongue ulcers: histological, immunohistochemical and biochemical study.

Caustic ingestion is a potentially detrimental event that can cause serious devastating damage on contact with tissues. Local exposure is associated with severe pain, swelling and ulceration. Caustics-induced oral ulcers can be painful enough to compromise the patient's quality of life. Treatment of oral ulcers is crucial in clinical practice. Albeit, some ulcers do not respond adequately to the conventional treatment. The current study was conducted to evaluate the potential healing effects of topical Salvadora persica (SP) extract, low-level laser (LLL) and high-level laser (HLL) therapies in a rabbit model of caustic-induced tongue ulcers and explore the underlying mechanisms. Fifty male rabbits with a caustic induced tongue ulcers were included in the study. Rabbits were equally divided into four groups: positive control (ulcer) group, SP, LLL and HLL groups in addition to the negative control (healthy) group. All treatments were given thrice weekly for 14 days. Results showed that acetic acid-induced tongue ulcers caused extensive structural tongue damage secondary to overexpression of apoptotic BAX, pathological angiogenesis indicated by VEGF overexpression, marked collagen fibers deposition as well as upregulation of tissue pro-inflammatory TNF-α and upregulation of tissue anti-inflammatory IL-10. The healing potential of topical SP, LLL and HLL therapy are mostly comparable. In conclusion, acetic acid-induced extensive tongue damage. Topical SP extract, LLL and HLL are equally effective therapies against caustics-induced tongue ulcers. However, we recommend SP extract, owing to its safety, non-invasiveness, availability and low cost.