Histological and biochemical studies on effect of Sofosbuvir (Sovaldi) on adult male albino rat kidney.

Sofosbuvir (sovaldi) is the backbone of many anti-HCV drugs. We aimed to demonstrate the effect of sofosbuvir on the adult male albino rat kidney. Sixty adult male albino rats were used. The animals were divided equally into 2 main groups (I and II), and each group was divided equally into 3 subgroups (A, B, and C). In group I (control group), each rat was gavaged 0.5 ml distilled water daily for 4 weeks. In group II (sofosbuvir treated group), each albino rat was gavaged 0.5 ml distilled water containing 7.2 mg sofosbuvir daily for 4 weeks. The rats were sacrificed at the end of the 4th week (subgroups IA and IIA), 6th week (subgroups IB and IIB), and 8th week (subgroups IC and IIC) from the start of the treatment. The kidneys were used for histological study while blood samples were used for biochemical study. The obtained data were statistically analyzed. Sofosbuvir (sovaldi) induced pathological changes that gave the criteria of acute Kidney injury in the adult male albino rats. The pathological changes were confirmed by elevation of serum level of urea and creatinine. After 2 and 4 weeks of drug withdrawal, the kidney incompletely recovered. We concluded that sofosbuvir induced criteria of acute tubular injury in the kidney of the adult male albino rats. This renal injury was proved by histological and biochemical studies. These insults were incompletely reversible after the end the treatment.

Mesenchymal stem cells enhance AQP1 expression in the sublingual salivary gland of ovariectomized menopausal rat model.

BACKGROUND: Ovariectomized menopausal rat model was used to investigate the effects of menopause on the sublingual salivary gland (SSG) and the potential therapeutic effect of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). METHODS: Thirty rats were equally divided into three groups: sham-operated (SHAM), ovariectomized (OVX), and ovariectomized stem cells injected (OVX+ hUCB-MSCs). Expressions of α-SMA, AQP1, Sca-1, PCNA, ssDNA, and caspase-3 were determined. Homing of hUCB-MSCs was detected by fluorescence microscopy and examination of immunostained sections for human CD105 and CD34 was performed. Morphometric data were statistically analyzed using the Kruskal-Wallis test followed by Scheffé's method. Correlation of AQP1 with Sca-1-positive sublingual stem cells was also analyzed. RESULTS: In the SSGs of the OVX group, ballooned mucus acinar cells, atrophied serous cells, and a decreased number and height of duct lining cells were observed. The interstitial spaces were edematous, and the blood vessels were congested. The significant decrease in the positive area % of α-SMA and AQP1, the number of Sca-1-positive sublingual stem cells, and proliferating cells was associated with a significant increase in apoptotic cells. The OVX+hUCB-MSCs group showed significant structural improvement, manifested by the normal appearance of mucus and serous acini, as well as the number and height of striated duct cells. A significant increase in the positive area % of α-SMA and AQP1 and the number of proliferating and Sca-1-positive sublingual stem cells was observed. Interestingly, a significantly positive Pearson's correlation between the area % of AQP1 and the number of Sca-1-positive sublingual stem cells was also recorded. CONCLUSION: Our results indicated a positive effect of hUCB-MSCs therapy for SSG pathology in a post ovariectomy rat model as evidenced by an improvement in the histologic architecture, upregulation of the immunostained area % of α-SMA and AQP1, increase in the number of Sca-1-positive sublingual stem cells and proliferating cells, and downregulation of apoptotic cells.

Hypoxia-Preconditioned Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Mitigate Hypoglycemic Testicular Injury Induced by Insulin in Rats.

Hypoglycemia is a neglected metabolic disorder. Thus, we evaluated the protective effect of hypoxia-preconditioned human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) on hypoglycemic testicular injury. We examined 56 testes from 28 animals: 7 rats with insulin-induced hypoglycemia (HG group), 7 hypoglycemic rats which received an intratesticular injection of hUCB-MSCs (HG-MSC group), and 14 untreated control rats. Testosterone level, testicular catalase (CAT) activity, and malondialdehyde (MDA) level were analyzed. Immunostaining for specific testicular germ and somatic cell markers was performed. Proliferating and apoptotic cells were detected by anti-PCNA and anti-caspase-3, respectively. Morphometrical data were statistically analyzed. The hypoglycemic rats showed a significant decrease in testosterone level and CAT activity and a significant increase in MDA production. Examination of histological structure and protein expression of diverse germ cell markers revealed collapsed tubules that were lined by degenerated germ cells, decreased lactate dehydrogenase type C immune expression, as well as decreased proliferating and increased apoptotic cells number in hypoglycemic testes. Injection of MSCs improved testicular biochemical parameters, preserved germ cells and somatic cells, and decreased apoptosis. In conclusion, hypoxia-preconditioned hUCB-MSCs attenuate rat testicular injury caused by insulin-induced hypoglycemia. Avoidance and rapid management of hypoglycemia are necessary to avoid significant testicular injury.

Triclosan treatment to pregnant albino rats affects offspring numbers and the liver of both the pregnant rats and their offspring, and these effects are ameliorated by co-treatment with bee honey.

We have assessed the effects of the broad-spectrum bactericide triclosan on the liver of pregnant albino rats and their offspring, and evaluated the protective potential of bee honey, which has radical-scavenging properties. The study involved treatment of 72 pregnant rats followed by examination of the pregnant rats and their offspring. The pregnant rats were divided equally into six groups (I-VI), each of which was subdivided equally into two Subgroups (A and B). Rats in the A subgroups were gavaged with a daily dose of 1.26 ml distilled water (IA), 1 ml corn oil (IIA), 1.68 ml aqueous solution of Clover Blossom honey (IIIA), 0.3 mg triclosan (IVA), 13 mg triclosan (VA), or 1.68 ml aqueous solution of honey with 13 mg triclosan (VIA), throughout pregnancy. Rats in the B subgroups received the same treatments throughout pregnancy and for 14 days after delivery. At the end of the experiments, the offspring's numbers were recorded and blood samples were taken from the pregnant rats for analysis. The livers of the studied groups were subjected for; histological study, morphometric analysis, and biochemical estimation of markers of oxidative stress. The results showed that the acceptable daily intake of triclosan did not induce significant pathological changes in the liver while high dose of triclosan induced pathological changes in the livers and reduced the numbers of offspring. Co-administration of honey with triclosan ameliorated most pathological change. Therefore, decrease the exposure of the pregnant women to triclosan is encouraged or co-supplementation with bee honey if exposure could not be avoided.

Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate the Pancreatic Changes of Chemically Induced Hypothyroidism by Carbimazole in Male Rats.

We induced hypothyroidism (HT) in male rats through chronic oral administration of carbimazole and then tested whether an i.v. injection of rat bone marrow-derived mesenchymal stem cells (BM-MSCs) could ameliorate the HT-induced changes in pancreatic structure and function. The thyroid and pancreatic function tests, as well as total antioxidant capacity (TAC) and malondialdehyde (MDA) were estimated. The pancreatic structure was evaluated by hematoxylin and eosin (H&E) stain. Insulin protein and cleaved caspase-3 were detected immunohistochemically. The degree of apoptosis was assessed by TUNEL assay. The morphometric measurements were done by an image analyzer system and the obtained data were statistically analyzed. HT rats showed hyperglycemia associated with insulin deficiency, decreased TAC and increased MDA levels. H&E-stained sections showed that the pancreatic septa were infiltrated with acidophilic material. Some acini were vacuolated while others showed depleted acidophilia and dilated lumina. Spindle-shaped cells were accumulated within deformed islets in HT rats. The positive reaction with anti-cleaved caspase-3 was exclusively noted in the cytoplasm of islet cells with no immunostaining reaction in the acinar and ductal cells, whereas the positively stained nuclei with TUNEL were demonstrated in the islet and acinar cells. A significant increase in the apoptotic index % of both markers was detected. Injection of BM-MSCs in HT rats restored all biochemical indicators of disturbed pancreatic function to normal level and improved pancreatic structure, resulting in a clear septa and normal appearance of acini and islets. In conclusion, many of the significant structural and func tional pancreatic alterations detected in HT rats were ameliorated after the injection of BM-MSCs. These data demonstrate the ability of BM-MSCs to repair pancreatic disturbances. Further studies on humans are necessary to determine the potential clinical applications of BM-MSCs.

Chemopreventive effect of Mentha piperita on dimethylbenz[a]anthracene and formaldehyde-induced tongue carcinogenesis in mice (histological and immunohistochemical study).

OBJECTIVE: Cancer chemoprevention is defined as the use of chemicals or dietary components to block, inhibit, or reverse the development of cancer in normal or pre-neoplastic tissue. Mentha extract (ME) has antioxidant and antiperoxidant properties. This study was held to investigate the protective and anticancer effect of Mentha leaves aqueous extract on oral epithelium of mice tongues. DESIGN: A total of 80 Egyptian albino mice were divided into three groups. Group I served as control (not subjected to any kind of treatment), and groups II and III were subjected to two-stage chemical carcinogenesis through topical application of dimethylbenz[a]anthracene (DMBA) followed by formaldehyde on dorsal and ventral surfaces of tongues for 9 weeks. Mentha leaves extract was administrated to group III at the same time of cancer induction. Histological changes were assessed in H&E sections at 3-week intervals. The anticarcinogenic effect of Mentha piperita was tested using immunostain with anticaspase antibody. RESULTS: The oral administration of ME reduced the appearance of dysplastic cellular changes with 61% and inhibited tumor incidence with 100%. Group I showed moderate-to-strong cytoplasmic caspase expression. At 6-week interval, group II showed weak-to-moderate caspase expression, while sections from group III showed moderate-to-strong caspase expression. High significant statistical difference in the total score of caspase 3 expression was found between specimens obtained from animals sacrificed at 6 weeks in groups I, II, and III (P = 0.001**). CONCLUSION: Our study demonstrated that Mentha piperita has inhibited the initiation and promotion of oral dysplastic lesions.