The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage

BACKGROUND@#The extracellular vesicles (EVs) secreted by bone marrow-derived mesenchymal stem cells (MSCs)hold significant potential as a novel alternative to whole-cell therapy. We herein compare the therapeutic potential of BMMSCsversus their EVs (MSC-EVs) in an experimental Carbon tetrachloride (CCl4)-induced liver damage rat model. @*METHODS@#Rats with liver damage received a single IV injection of MSC-EVs, 1 million MSCs, or 3 million MSCs. Thetherapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistryfor liver fibrosis and hepatocellular injury. @*RESULTS@#Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression ofcollagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and functionally. @*CONCLUSION@#Similar to high doses of MSC-based therapy (3 million MSCs), MSC-EVs mitigated the fibrogenesis andhepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuatinghepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-freetherapeutic strategy for liver fibrosis and hepatocellular damage.

The Therapeutic Potential of Extracellular Vesicles Versus Mesenchymal Stem Cells in Liver Damage

BACKGROUND@#The extracellular vesicles (EVs) secreted by bone marrow-derived mesenchymal stem cells (MSCs)hold significant potential as a novel alternative to whole-cell therapy. We herein compare the therapeutic potential of BMMSCsversus their EVs (MSC-EVs) in an experimental Carbon tetrachloride (CCl4)-induced liver damage rat model. @*METHODS@#Rats with liver damage received a single IV injection of MSC-EVs, 1 million MSCs, or 3 million MSCs. Thetherapeutic efficacy of each treatment was assessed using liver histopathology, liver function tests and immunohistochemistryfor liver fibrosis and hepatocellular injury. @*RESULTS@#Animals that received an injection of either MSCs-EVs or 3 million MSCs depicted significant regression ofcollagen deposition in the liver tissue and marked attenuation of hepatocellular damage, both structurally and functionally. @*CONCLUSION@#Similar to high doses of MSC-based therapy (3 million MSCs), MSC-EVs mitigated the fibrogenesis andhepatocellular injury in a rat model of CCl4-induced liver fibrosis. The anti-fibrinogenic effect was induced by attenuatinghepatic stellate cell activation. Therefore, the administration of MSC-EVs could be considered as a candidate cell-freetherapeutic strategy for liver fibrosis and hepatocellular damage.

possible role for gastroprotectives on aspirin-induced gastric ulcer in rats

Gastric ulcer is a discontinuity in the gastric mucosa that occurs due to imbalance between gastric mucosal protective factors and aggressive factors. The Aim of the present work was to test and compare the protective effects of an antisecretory H2 receptor blocker; ranitidine and other recently suggested gastroprotective drugs: L-arginine; a precursor of NO, zinc sulfate; an anti-inflammatory antioxidant agent and pioglitazone; a PPAR-gamma agonist, on a rat model of aspirin induced gastric ulcer. Acute gastric lesion was induced in rats by a single oral dose of aspirin 300mg/ kg body weight. L-arginine 200mg / kg b. wt, zinc sulfate 80 mg/ kg b. wt, and pioglitazone 10 mg / kg b. wt. were given alone and in combination with ranitidine 50 mg / kg b. wt for 3 days before induction of gastric lesion. Aspirin induced a significant increase in gastric mucosal lesion score and free and total gastric hydrochloric acid with a significant decrease in gastric nitric oxide and mucin levels as compared to normal group. A significant increase in gastric malondialdhyde and decrease in reduced glutathione as compared to normal group. L-arginine, zinc sulfate, and pioglitazone produced improvement of most of the measured parameters as compared to non-treated group. Combination of L-arginine and ranitidine was superior in prophylaxis against aspirin-induced gastric ulcer when compared to the effects of each drug used individually, and the other studied combinations. The role of HCl and NO seems more important in the pathogenesis of aspirin induced gastric ulcer, as evidenced by the better protective effects of combination of ranitidine and L-arginine in comparison to the ranitidine with either zinc sulfate or pioglitazone

Histological changes in the filiform and fungiform lingual papillae of streptozotocin-induced diabetic albino rats and the possible protective role of curcumin

It has been a growing interest recently in dietary intervention, particularly the use of traditional food derived from natural sources in management of diabetic complications as oral lesions. The aim of the present study was to elucidate the histological changes in the lingual papillae in an experimental model of induced diabetes in rats by streptozotocin and evaluate the possible protective effect of curcumin using light and scanning electron microscopes. Thirty adult male albino rats were divided into 3 equal groups: group 1; [control group], group II;[diabetic group]: diabetes was induced by a single intraperitoneal injection of streptozotocin in a dose of 65 mg/kg and group [Unprotected group] rats were treated as in diabetic group with simultaneous administration of' curcumin in a daily dietary dose of 15 mg/kg for 4 weeks. By the end of the 4 weeks all animals were sacrificed and the tongues of all rats were dissected and processed for light and scanning electron microscopic examination. Examination of dorsal surface of tongues of diabetic rats revealed numerous filiform papillae with evidently disturbed shape and orientation. Some of them depicted notched or bifurcated ends; others were severely destroyed with desquamation of their epithelial covering. There were hyperkeratosis and markedly reduced connective tissue papillae. Disfigured fungiform papillae with vacuolated taste buds depicting peripheral arrangement of the cells and empty center were also seen. Dorsal surface rats' tongues of the protected group with curcumin revealed almost normal direction, distribution and structure of the papillae except for few filiform papillae with serrated tips. The present study illustrated that diabetes has a deleterious effect on tongue papillae and taste buds. On the other hand, curcumin provided considerable protection against these effects most probably via its antioxidant, anti-inflammatory and neuroprotective effects

Protection against acute adriamycin-induced cardiotoxicity by nigella sativa oil, thymoquinone, garlic extract and COQ[10] in rats

Oxidative stress is a major etiologic factor in adriamycin [ADR]-induced cardiotoxicity that limits the clinical efficacy of this anticancer drug. Since, many beneficial health-related biological properties are attributed to Nigella sativa L. oil [NSO], thymoquinone [TQ], garlic, and Coenzyme Q-10, the present study examined the cardioprotective effect of these remedies against ADR-induced cardiotoxicity. The study was carried out on 110 male Albino rats. They were divided into a control group [10 rats] and 5 groups of ADR-treated rats [n=20 in each] as follows: [i] ADR, [ii] CoQ10+ADR [iii] NSO+ADR [iv] Garlic+ADR and [v] TQ+ADR groups. Administration of CoQ10, NSO, garlic, and TQ were started one week prior to ADR and continued once daily thereafter for the next 2 weeks. The assessment of cardiac affection was carried out by measuring the level of serum creatine kinase [CK] and lactate dehydrogenase [LDH]. Also, activities of superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPX], cytosolic aconitase [c-aconitase] as well as the malondialdehyde [MDA] and cell iron content were measured in myocardial tissue homogenate. Moreover, light and electron microscopic changes were scored. The administration of ADR to the experimental rats produced wide range of changes. A significant decrease in activities of the antioxidant enzymes SOD, CAT and GPX in ADR-treated rats was found compared to normal control values. Also, myocardial MDA level was significantly high as well as serum LDH and CK denoting myocardial injury. The ADR-treated rats also showed significant inhibition of myocardial c-aconitase activity and rise of cell iron content compared to control myocardium. The histological results of this group revealed hypereosinophilia, myofibrillar damage, nuclear abnormalities, mitochondrial degeneration and diminished glycogen. Neither CoQ10 nor the whole oil of nigella sativa significantly modified ADR-induced impairment in SOD, GPX or CAT activity. CK was significantly less elevated in the NSO but insignificantly different in the CoQ10 while LDH was significantly less elevated in both groups compared to ADR group. Activity of c-aconitase was significantly higher in NSO than CoQ10 and ADR groups while cellular iron was insignificantly different. Also, survival was significantly improved in the NSO but not in the CoQ10 compared to ADR group. These findings were further documented by the histological findings. Examination of ADR-CoQ[10] treated rats showed extensive cellular damage including the mitochondria, intercalated discs, the cytoskeleton, the nuclei and diminished glycogen deposition. Conversely, 3 weeks administration of TQ and garlic in the present study have yielded encouraging results against acute ADR-induced cardiotoxicity in rats, as indicated by 100% survival rate which was found in these groups versus 40-50% in the ADR and CoQ10 treated groups. Moreover, they have been associated with: conserved activity of myocardial antioxidant enzymes GPX, SOD and CAT with suppression of MDA formation and less accumulation of cellular iron compared to ADR, CoQ10 and NSO treated groups. The histological results further proved this results and revealed high degree of myocardial protection in TQ-treated rats and garlic-treated rats respectively where the most examined myocytes were nearly normal. Thymoquinone [TQ] and garlic had shown significant cardioprotective effect much superior to NSO and CoQ10 against ADR-induced myocardial toxicity. The low TQ content in the chosen dose of NSO could be the underlying cause of lacking therapeutic effect although a strong antioxidant effect have been recently reported with this dose of NSO. Hence, a larger dose of NSO and probably of CoQ10 can be subjected to further study for protection against ADR-induced cardiac injury

Histological study of the possible toxic effect of selenium on the thyroid follicular cells of albino rats

Selenium is a trace element, essential in small amounts, but it can be toxic in larger amounts. Selenium compounds are widely used as a dietary supplement and as a prophylaxis for the prevention of cancer, cardiovascular diseases and viral mutations. However, there is a narrow margin between safe therapeutic and toxic doses of selenium. The goal of the present study was to study the histological effect of the adequate and toxic doses of selenium on the follicular cells of thyroid gland of albino rats. The study was carried out on 30 adult male albino rats weighing 120-150 gm. Animals were divided into 3 equal groups: Control group; which received adequate diet but without the addition of selenium. Group I [supplemented group]: received sodium selenite in a dose of 75 microgram / kg b.w., and group II [Intoxicated group]: received sodium selenite in a dose of 300 microgram /kg bw. Histological examination of the semithin and ultrathin sections of the supplemented group [group I] revealed nearly normal control image in most of the examined thyroid follicles. Few follicles showed some follicular cells with vacuolated cytoplasm and many dense bodies and others showed irregular nuclei. Ultrastructural examination revealed some cells with dilated cisternae of rough endoplasmic reticulum, widened intercellular spaces and the infiltration of the interstitial spaces with some inflammatory cells and excessive collagen deposition. Histological examination of the intoxicated group [group II] revealed hypertrophy and hyperplasia of the thyroid follicles which appeared crowded with minimal interfollicular spaces. Some follicles showed stratification of their lining cells while others showed dome shaped cells with vacuolated cytoplasm and many dense bodies. Numerous basal and lateral cytoplasmic processes, interrupted epithelial lining and exfoliated cells in the lumina were frequently encountered. The present work recommend the intake of natural diet enriched with high content of selenium and warn about daily intake of exceeding doses of selenium supplementations

Pharmacological, histological and immunohistochemical study of the induced osteoporotic changes in ovariectomized rats and possible protective and therapeutic effects of rofecoxib and indomethacin

The aim of this study was to assess the possible modulatory effects of rofecoxib [selective cyclooxygenase -2 inhibitor], and indomethacin [non-selective cyclooxygenase inhibitor], on the development of osteoporosis in experimentally induced postmenopausal osteoporosis in female rats. This study was carried out on sixty-four adult female albino rats weighing 180-190 grams of nine months of age. Under light ether anesthesia, the rats underwent ovariectomy [OVX] or Sham operation by the dorsal approach and assigned to eight groups of eight rats each. Group 1: Sham operated and treated with vehicle and served as a control for groups 2-4. Groups 2, 3 and 4: OVX treated with; vehicle, rofecoxib [3mg/kg BW/day] and indomethacin [1mg/kg BW/day] respectively. Groups 1-4 were given vehicle or respective drugs daily orally for six weeks through gavage starting immediately after OVX. Group 5: Sham operated and treated with vehicle and served as a control for groups 6-8. Groups 6, 7 and 8: OVX treated with; vehicle, rofecoxib [3mg/kg BW/day] and indomethacin [1mg/kg BW/day] respectively. Groups 5-8 were given vehicle or the respective drugs daily orally through gavage started at the sixth week after OVX and continued for consecutive six weeks. At the end of the experiment period, six weeks of groups 1-4 and twelve weeks for groups 5-8, 24 hours urine was collected after the last treatment for estimation of urinary hydroxyproline and calcium. Under light ether anesthesia blood samples were collected from the retro-orbital venous plexus. Sera were separated for estimation of osteocalcin, bone specific alkaline phosphatase and serum calcium. Then, the animals were sacrificed and the lumbar vertebrae and both femurs were excised for histological and immunohistochemical studies. The present study demonstrated that estrogen deficiency induced by OVX was clearly associated with increased bone turnover. The bone resorption was manifested by a significant increase in the mean value of urinary hydroxyproline, and urinary calcium excretion, thinning of bone trabeculae, widening of bone lamellae, anastmosis of bone marrow cavities and decreased expression of collagen type I staining. The trabecular bone was affected earlier and to a greater extent than long cortical bone. Bone formation was also evident by a significant increase in the mean value of serum osteocalcin, bone specific alkaline phosphatase and a significant decrease in mean value of serum calcium, presence of many osteogenic cells at the periosteal and endosteal surface, multiple cement lines and random orientation of less flattened osteocyte's lacunae. There was no significant difference between the mean values of the studied parameters in the vehicle treated ovariectomized groups at the 6[th] and 12[th] weeks after OVX. Immediate administration of rofecoxib [but not indomethacin] after OVX produced remarkable protective effect on the development of osteoporosis as manifested by decreased bone turnover markers and normal histological and immunohistochemical structure. On the other hand, administration of either rofecoxcib or indomethacin six weeks after OVX for another consecutive six weeks failed to produce significant protective effect but improve the quality of the newly formed bones. Selective cyclooxygenase -2 inhibitors are recommended early during development of osteoporosis as they have a protective effect on bone resorption. Nonsteroidal anti-inflammatory drugs [either selective or non-selective] would be beneficial when given after the development of osteoporosis as they improve the quality of the newly formed bones