Improvement Of Histopathological Changes Research Articles

Naturally occurring phytanic acid exerts anti‐inflammatory effects in a mouse model of dextran sulfate sodium‐induced colitis

AbstractPhytanic acid is one of the branched‐chain fatty acids in the human diet. Humans incorporate it into their bodies through the ingestion of ruminant meat and milk since these animal products contain the 3RS, 7R, 11R‐isomer, as naturally occurring phytanic acid (nPA). Although phytanic acid has been reported to have health‐promoting effects such as immunomodulatory effects, these findings were obtained mostly from in vitro cell‐based experiments. In this study, the in vivo anti‐inflammatory effects of nPA were investigated using a mouse model of dextran sulfate sodium (DSS)‐induced colitis. Mice were fed diets containing 0%, 0.05%, or 0.1% nPA for 4 weeks. During the fourth week, acute colitis was induced by administration of a 3% DSS solution. The intake of 0.05% and 0.1% nPA inhibited DSS‐induced body weight loss in mice, and showed improvement of histopathological changes in colon epithelium. nPA also inhibited the production of proinflammatory cytokines, especially macrophage‐related cytokines such as interleukin‐1β in the colon. These results suggest that nPA exerts anti‐inflammatory effects under in vivo physiological conditions.Practical application: There is a growing demand for fatty acids possessing distinct nutritional and physical characteristics in the realms of health, nutrition, and food‐related applications. The present study demonstrated that a branched‐chain fatty acid, phytanic acid, exerts anti‐inflammatory activity under not only in vitro but also in vivo conditions, using a commonly used mouse model of human inflammatory bowel disease. Our findings encourage further studies to determine whether phytanic acid elicits beneficial properties in humans, and suggest that phytanic acid enrichment can be a novel product strategy in the food market.

A Comparative Study to Examine the Effects of Topical Vinpocetine and Tacrolimus on Induced Atopic Dermatitis in Mice.

Background: Atopic dermatitis (AD) is a persistent and recurring inflammatory skin disorder distinguished by parched skin and severe itching. The pathogenesis of AD involves increased production of specific cytokines, such as Interlukin-4 (IL-4) and Interlukin-13 (IL-13), which are associated with the T helper 2 pathway. However, prolonged use of the current glucocorticoids and calcineurin inhibitors medications can lead to adverse effects. Aim of the study: To assess the efficiency of topical Vinpocetine and Tacrolimus in treating an induced atopic dermatitis mice model. Methods: Five sets of fifty male Albino mice, were randomly selected. One-chloro-2,4-dinitrobenzene (DNCB) was applied to the dorsal (back) skin of forty mice to cause atopic dermatitis. Ten control healthy mice were placed in Group I, ten mice with atopic dermatitis were placed in Group II; neither group received any treatment. Group III consists of 10 mice that received tacrolimus 0.1% ointment, group IV was administered a topical ointment comprising 5% Vinpocetine and lastly, group V underwent a vehicle ointment. Severity was assessed visually, IL-4 and IL-13 were measured by immunohistochemistry, in addition to general histopathological evaluation as well as examining WBCs. Results: The groups treated with Vinpocetine 5%, and Tacrolimus all had significantly lower levels of WBC counts, decreased IL-4 and IL-13 staining according to immunohistochemistry and lower histopathological scores. Vinpocetine 5% and tacrolimus treatment also showed a statistically significant reduction in hyperkeratosis and inflammation among the studied groups (P<0.001). Conclusions Topical Vinpocetine 5% ointment, and tacrolimus 0.1% were effective in the treatment of induced AD mouse model through the improvement of histopathological changes and their ability to decrease IL-4 and IL-13, Vinpocetine were effective in the treatment of induced AD. Keywords: Atopic dermatitis, Tacrolimus, Topical, Vinpocetine.

Modulation of CXCL10 activity as a therapeutic target of ocular toxoplasmosis in diabetic mice.

Ocular toxoplasmosis is likely the most common cause of infectious posterior uveitis worldwide. CXCL10 chemokine has an important role in the maintenance of the T-cell response and the control of Toxoplasma gondii in the eye during chronic infection. Drugs that can modulate the chemokine activity could be effective against the parasite. In this work, CXCL10 local retinal expression was investigated in a diabetic mouse model with ocular toxoplasmosis for the first time. In addition, the efficacy of naphthoquinones and quinolones was compared to spiramycin (SP) in treating the infection and modulating the chemokine expression. Our results revealed that chloroquine (CQ) achieved the best results regarding the reduction of cerebral cyst burden (84.36%), improving the retinal histopathological changes, cellular infiltrates, and vasculitis significantly (P < 0.005), and balancing the strong CXCL10 expression caused by the infection. Buparvaquone-treated mice showed a significant percentage of reduction of brain cysts (76.25%), moderate improvement of histopathology, and mild to moderate CXCL10 expression. While SP showed the least efficacy against the parasite in the eye in the form of mild improvement of histopathological changes and downregulation of retinal chemokine expression with the least reduction rate of cerebral parasitic burden (57%). In conclusion, Optimal control of pathogens probably needs a balanced immune response with an optimum expression of chemokines. So, targeting the modulation of retinal CXCL10 may eventually be beneficial in the management of ocular toxoplasmosis plus its potential to act as a marker for predictive local immunological response during the infection.

Agomelatine alleviates steroid-induced osteoporosis by targeting SIRT1/RANKL/FOXO1/OPG signalling in rats.

One of the major contributors to secondary osteoporosis is long-term glucocorticoid usage. Clinically used antidepressant agomelatine also has anti-inflammatory properties. Our research aimed to inspect the probable defensive effect of agomelatine against steroid-promoted osteoporosis. There were four groups of rats; group I had saline as a negative control; rats of group II had dexamethasone (0.6 mg/kg, s.c.), twice weekly for 12 weeks; rats of group III had agomelatine (40 mg/kg/day, orally), as a positive control, daily for 12 weeks; and rats of group IV had dexamethasone + agomelatine in the same previous doses combined for 12 weeks. Finally, biochemical as well as histopathological changes were evaluated and dexamethasone treatment caused osteoporosis, as evidenced by discontinuous thin cancellous bone trabeculae, minor fissures and fractures, irregular eroded endosteal surface with elevated alkaline phosphate, tartarate resistant acid phosphate (TRACP) and osteocalcin levels. Osteoprotegerin (OPG), calcium, and phosphorus levels decreased with disturbed receptor activator of nuclear factor κ B ligand (RANKL), forkhead box O1 (FOXO1), and silent information regulator 1 (SIRT1)protein expression. However, treatment with agomelatine restored the normal levels of biochemical parameters to a great extent, supported by SIRT activation with an improvement in histopathological changes. Here, we concluded that agomelatine ameliorates steroid-induced osteoporosis through a SIRT1/RANKL/FOXO1/OPG-dependent pathway.

Effect of a TNF-Alpha Inhibitor on Anxiety and Depression-Like Behaviors in a Mouse Chemobrain Model

Although chemotherapy increases the survival rate of cancer patients, it causes significant side effects such as deterioration in cognitive functions that generate a decline in their living standards. In our study, the effect of adalimumab on anxiety- and depression-like behaviors in mice with cognitive impairment with methotrexate was investigated. In our study, methotrexate (40 mg kg-1) was administered intraperitoneally as a single dose to create a chemobrain model in mice. Adalimumab (10 mg kg-1), a TNF-alpha inhibitor, was administered twice, 1 hour and 5 days before methotrexate administration. Anxiety-like behaviors were measured with elevated plus maze test and open field test, depression-like behaviors were measured with tail suspension test, and hippocampal tissue was examined histopathologically. Methotrexate decreased the time spent in the central zone in the open-field arena, the time spent in the open arms in the elevated plus maze test, and increased the duration of immobility in the tail suspension test in rats. Methotrexate caused a decrease in the number of neuronal cells in the CA3 region of the hippocampus, as well as neurodegenerative and atrophic changes. Adalimumab ameliorated methotrexate-related anxiety- and depression-like behaviors, and caused improvement in histopathological changes. In this study, it was shown that methotrexate-related anxiety and depression-like behavioral disorders were prevented by adalimumab treatment, but further studies are recommended to investigate the mechanisms mediating the therapeutic effect of adalimumab.

Metabolite profiling and Ameliorative effect of quince (Cydonia oblonga) leaves against doxorubicin induced cardiotoxicity in Wistar rats

Quince (Cydonia oblonga) leaves are traditionally reported to alleviate the risk of cardiovascular disease. The study envisaged to explore the in vitro and in vivo phytochemical and cardio protective potential of quince extract respectively. Different solvent extracts (Aqueous, Ethanolic, Hydroethanolic, Methanolic) of quince leaf obtained via two different extraction methods (Ultrasonication and Reflux) were evaluated for the phytochemical and antioxidant analysis. Among all the extracts, quince ethanolic extract, extracted via sonication was found to have the maximum phenolics (39.89 ± 0.67 mg GAE/g DW), flavonoids (21.51 ± 1.0 mgRE/g DW) and an anti-oxidant potential 2,2-diphenyl-1-picryl-hydrazyl radical (DPPH) with IC50 value of 168.88 ± 2.24 μg/ml. The High-performance thin layer chromatograph (HPTLC) and ultrahigh performance liquid chromatography mass spectrometry (UPLC-MS) analysis confirmed the presence of bio active compounds. Furthermore, the in vivo activity was ascertained against Doxorubicin (DOX) induced cardio toxicity in rats fed orally with the extract at 160 and 320 mg/kg body weight. The pre-treated groups significantly assuaged the changes induced by DOX in the electrocardiogram (ECG). Additionally, it mitigated the elevation in the blood serum parameters; aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine kinase-MB (CK- MB) and also repressed glutathione (GSH) depletion and rise in malondialdehyde (MDA) level induced by DOX. Furthermore, improvement in histopathological changes of the heart tissue concomitant to DOX induced toxicity was also observed such as, reduced degeneration, necrosis, inflammation and apoptosis. Thus, it could be concluded that cardioprotective activity of quince extract accredited to the occurrence of phytoconstituents prevented the DOX induced cardiotoxicity and helped to reinstate the cardiac damage in rats.

Hepatoprotective potential of Tamarindus indica following prenatal aluminum exposure in Wistar rat pups.

Over time, the use of plant-derived agents in the management of various human health conditions has gained a lot of attention. The study assessed the hepatoprotective potential of ethyl acetate fraction Tamarindus indica leaves (EFTI) during prenatal aluminum chloride exposure. Pregnant rats were divided into 5 groups (n=4); Group I rats were administered 2mlkg-1 of distilled water (negative control), Group II rats received only 200mgkg-1 aluminum chloride (positive control), Group III rats were administered 200mgkg-1 aluminum chloride and 400mgkg-1 EFTI, Group IV rats were administered 200mgkg-1 aluminum chloride and 800mgkg-1 EFTI, Group V rats were administered 200mgkg-1 aluminum chloride and 300mgkg-1 Vit E (comparative control). On postnatal day 1, the pups were euthanized, and liver tissues were harvested for the biochemical study (tissue levels of malondialdehyde, caspase-3, tumor necrosis factor-alpha, aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferases) and the liver histological examination. The administration of EFTI was marked with significant improvement in the tissue levels of malondialdehyde, caspase-3, tumor necrosis factor-alpha, aspartate aminotransferase, alkaline phosphatase, and alanine aminotransferases. There was a marked improvement in histopathological changes associated with prenatal aluminum chloride exposure. In conclusion, the administration of EFTI was protective during prenatal aluminum chloride exposure of the liver in Wistar rats, and is mediated by the anti-lipid peroxidative, antiapoptotic, and anti-inflammatory activity of EFTI.

Genistein attenuated oxidative stress, inflammation, and apoptosis in L-arginine induced acute pancreatitis in mice

AimAcute pancreatitis is a common and potentially serious condition. However, a specific treatment for this condition is still lacking. Genistein, with its anti-oxidant and anti-inflammatory effects, could possibly be used to tackle the underlying pathophysiology of acute pancreatitis. Therefore, the aim of this study was to investigate the effects of genistein on oxidative stress, inflammation, and apoptosis in acute pancreatitis induced by L-arginine in mice.MethodsTwenty-four male ICR mice were equally divided into 4 groups: Control (Con); Acute pancreatitis (AP) group: Two doses of i.p. 350 mg/100 g body weight (BW) of L-arginine were administered 1 h apart; AP and low-dose genistein (LG) group: mice were given i.p. injection of 10 mg/kg genistein 2 h prior to L-arginine injection followed by once-daily dosing for 3 days; and AP and high-dose genistein (HG) group: mice were given 100 mg/kg genistein with the similar protocol as the LG group. Pancreatic tissue was evaluated for histopathological changes and acinar cell apoptosis, malondialdehyde (MDA) levels, immunohistochemical staining for myeloperoxidase (MPO), nuclear factor-kappa beta (NF-kB), and 4-hydroxynonenal (4-HNE). Serum levels of amylase (AMY), c-reactive protein (CRP), and interleukin (IL)-6 were measured.ResultsSignificant increases in the degree of acinar cell apoptosis, pancreatic MDA, serum IL-6 and amylase, MPO, NF-kB and 4-HNE positivity were observed in the AP group. All these parameters declined after low- and high-dose genistein treatment. Severe pancreatic inflammation, edema, and acinar cell necrosis were observed in the AP group. Significant improvement of histopathological changes was seen in both low- and high-dose genistein groups. There were no significant differences in any parameters between low and high doses of genistein.ConclusionGenistein could attenuate the severity of histopathological changes in acute pancreatitis through its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.

Angiotensin receptor-neprilysin inhibitor (thiorphan/irbesartan) improved cardiac function in a rat model of myocardial ischemic reperfusion injury.

Mitochondria-mediated apoptosis plays a critical role in myocardial ischemia reperfusion (IR) injury and causes a negative impact on cardiac efficiency and function. The combined angiotensin receptor-neprilysin inhibitor (ARNI) is a promising cardioprotective pharmacological agent that could rescue the heart from IR injury. This study investigated the cardioprotective effect of thiorphan (TH) in combination with three different doses of irbesartan (IRB) on myocardial IR injury and detected the most effective dose combination. Male Wistar rats were used and divided into five groups (10 rats/group): (I) Sham, (II) ischemia-reperfusion I/R, (III) TH/IRB + IR (0.1/5mg/kg), (IV) TH/IRB + IR (0.1/10mg/kg), and (V) TH/IRB + IR (0.1/15 mg/kg) groups. Thiorphan and irbesartan were injected intraperitoneally 15 min before IR induction. Mean arterial blood pressure, left ventricular end diastolic pressure (LVEDP), left ventricular maximum rate of pressure (LVdp/dtmax ), and cardiac levels of creatine kinase-MB, malondialdehyde, superoxide dismutase, and endothelin-1 were measured. Cardiac mitochondria complexes activities, histopathological examination of myocardial tissues, immunohistochemistry studies for myocardial apoptosis (Bax and Bcl-2), and electron microscopy examination of left ventricle were performed. TH/IRB combination preserved cardiac functions and mitochondria complex activities and mitigated cardiac damage, oxidative stress, and apoptosis following IR. Also, there was an evident improvement in histopathological changes and electron microscopy examination of left ventricle compared with I/R group. TH/IRB in a dose of 0.1/10mg/kg showed significant improvement compared with the other treated groups. Thiorphan/irbesartan improved cardiac functions following IR injury. This could be explained by the reported improvement of mitochondria complex activities and reduction of oxidative stress, endothelin-1, and apoptosis.

Apoptotic changes in the intestinal epithelium of Cryptosporidium-infected mice after silver nanoparticles treatment versus nitazoxanide.

Cryptosporidium has been identified as one of the prevalent opportunistic parasites that cause diarrhea, which may be persistent and fatal. Current chemotherapeutic agents, including nitazoxanide (NTZ), are frequently associated with therapeutic failure, and their roles in the induction of apoptosis in cryptosporidiosis remain to be a topic of debate. Thus, this study aimed to assess the apoptotic changes in cryptosporidiosis in immunocompetent (IC) and immunosuppressed (IS) mice after treatment with silver nanoparticles (AgNPs) and NTZ either alone or after loading. In total, 120 laboratory-bred Swiss albino mice were divided into two groups. Group A included IC mice, while Group B included IS mice. Both groups were divided into six subgroups: noninfected nontreated, infected nontreated, infected AgNP-treated, infected NTZ-treated, infected AgNP-loaded NTZ (full-dose)-treated, and infected AgNP-loaded NTZ (half-dose)-treated. The assessment was achieved through parasitological, histopathological, and apoptotic marker expression evaluation. AgNP-loaded NTZ (different doses) treatment showed the highest oocyst shedding reduction and remarkable improvement in histopathological changes, followed by individual treatment with NTZ and then AgNPs in IC and IS mice. Results of apoptotic marker expression revealed that AgNP-loaded NTZ treatment exhibited a promising role in regulating apoptotic changes in cryptosporidiosis through the expression of the lowest levels of cytochrome C and caspase-3 in IC and IS mice at the end of the experiment. Therefore, AgNP-loaded NTZ can be a potential therapeutic agent against cryptosporidiosis for IC and IS mice.

Antiproliferative activity of Brassica nigra seeds extract in liver tissue of mice exposed to phenobarbital

Hepatocellular proliferation is one of the most common causes of hepatocellular carcinoma (HCC), a type of cancer that is widely distributed disease. Hepatocellular carcinoma treatment has numerous barriers, including ineffectiveness, side effects, and drug resistance to currently available treatments. Previous studies showed that a high intake of Brassica vegetables has been associated to a decreased risk of a number of malignancies. The aim of this study is the evaluation of antiproliferative activity of Brassica nigra seeds extract in mice exposed to phenobarbital. Brassica nigra seeds where extracted; phytochemical analysis of the extract was done that including phytochemical screening tests and Gas chromatography-mass spectrometry (GC-MS) analysis. Antiproliferative activity of hydro alcoholic Brassica seeds extract has been studied by 800mg/kg and compare with control group (given normal saline), phenobarbital group (Phenobarbital 75mg/kg) and combination group (Brassica extract 800mg/kg+ Phenobarbital 75mg/kg). The GC-MS analysis revealed the presence of isothiocynate compound. Histologically phenobarbital induced severe hepatocellular proliferation (hyperplasia and hypertrophy), glass ground cytoplasm, while Brassica seeds extract produce improvement in histopathological changes that include mild scattered proliferation picture and eosinophilic cytoplasm. In comparison to phenobarbital group, Combination groups pretreated with Brassica nigra seeds for 14 days and phenobarbital for 7 days caused significant reduction relative liver weight and alanine aminotransferase (ALT) Brassica nigra seeds extract have isothiocynate as main compound it showed antiproliferative action on the liver tissue, implying that it may have a promising effect in minimizing the risk of liver cancer.

Molecular Mechanisms of Hawthorn Extracts in Multiple Organs Disorders in Underlying of Diabetes: A Review.

Diabetes mellitus (DM) is one of the most important metabolic disorders associated with chronic hyperglycemia and occurs when the body cannot manage insulin secretion, insulin action, or both. Autoimmune destruction of pancreatic beta cells and insulin resistance are the major pathophysiological factors of types 1 and 2 of DM, respectively. Prolonged hyperglycemia leads to multiple organs dysfunctions, including nephropathy, neuropathy, cardiomyopathy, gastropathy, and micro- and macrovascular disorders. The basis of the metabolic abnormalities in carbohydrate, fat, and protein in diabetes is insufficient action of insulin on various target tissues. Medicinal plants are rich sources of bioactive chemical compounds with therapeutic effects. The beneficial effects of leaves, fruits, and flowers extracts of Crataegus oxyacantha, commonly called hawthorn, belonging to the Rosaceae family, are widely used as hawthorn-derived medicines. Data in this review have been collected from the scientific articles published in databases such as Science Direct, Scopus, PubMed, Web of Science, and Scientific Information Database from 2000 to 2021. Based on this review, hawthorn extracts appear both therapeutic and protective effects against diabetic-related complications in various organs through molecular mechanisms, such as decreasing triglyceride, cholesterol, very low density lipoprotein and increasing the antioxidant activity of superoxide dismutase, catalase, glutathione peroxidase, total antioxidant capacity, decreasing malondialdehyde level, and attenuating tumor necrosis factor alpha, interleukin 6 and sirtuin 1/AMP-activated protein kinase (AMPK)/nuclear factor kappa B (NF-κB) pathway and increasing the phosphorylation of glucose transporter 4, insulin receptor substrate 1, AKT and phosphoinositide 3-kinases, and attenuating blood sugar and regulation of insulin secretion, insulin resistance, and improvement of histopathological changes in pancreatic beta cells. Collectively, hawthorn can be considered as one new target for the research and development of innovative drugs for the prevention or treatment of DM and related problems.

Nephroprotective effects of 4-4(hydroxyl-3 methoxyphenyl)-2-butane against sodium tellurite induced acute kidney dysfunction by attenuating oxidative stress and inflammatory cytokines in rats

The aim of this study was to elucidate the protective action mechanism of 4-4(hydroxyl-3-methoxyphenyl)-2-butane against Sodium tellurite (ST) induced nephrotoxicity in rats. ST is a hazardous substance used in metallurgical and glassware industries, but its renal toxicities have not been well established before. Rats were distributed into four groups, six rats contain in each group. Normal control group given only vehicles only, toxic group given ST 8.5 mg/kg p o, treated groups given ST and 4-(hydroxyl-3-methoxyphenyl)-2-butane(100 mg/kg bwt), and positive control given only treatment drug 4-(hydroxyl-3-methoxyphenyl)-2-butane (100 mg/kg bwt) daily for 14 days. ST administration increases an alteration in biochemical, oxidative stress, cytokines markers, and morphological changes in toxic group. When it was treated with 4-(hydroxyl-3- methoxyphenyl)-2-butane significantly (p < 0.5) restores all these changes such as biochemical markers, antioxidant, inflammatory cytokines, and histopathological improvements in treated group as compared to toxic group. No significant (p > 0.05) changes have been seen in positive control as compared to normal control. In conclusion, 4(hydroxyl-3 methoxyphenyl)-2-butane successfully defended the kidney from oxidative stress, inflammatory cytokines and necrosis against ST intoxication. Thus, significant improvements were reflected and confirms with the improvement in histopathological changes.

Combination of Vitamin C and Curcumin Safeguards Against Methotrexate-Induced Acute Liver Injury in Mice by Synergistic Antioxidant Effects.

Methotrexate (MTX), an antineoplastic and immunosuppressive drug, widely used in the treatment of different types of cancers and the management of chronic inflammatory diseases. However, its use is associated with hepatotoxicity. Vitamin C (VC) and curcumin (CUR) exhibit anti-inflammatory and antioxidant effects. Thus, we aimed to investigate the potential hepatoprotective effects of VC and CUR pretreatment alone and in combination against MTX-induced hepatotoxicity. Albino mice were randomly divided into 7 groups: the control group, which received only normal saline; MTX group; VC group, pretreated with VC (100 or 200 mg/kg/day orally) for 10 days; CUR group, pretreated with CUR (10 or 20 mg/kg/day orally); and combination group, which received VC (100 mg/kg) and CUR (10 mg/kg). MTX was administered (20 mg/kg, intraperitoneally) to all the groups on the tenth day to induce hepatotoxicity. Forty eight hours after MTX administration, the mice were anesthetized. Blood samples were collected, the liver was removed for biochemical analysis, and a part of the tissue was preserved in formalin for histopathological analysis. The results indicated that pretreatment with a combination of VC and CUR induced a more significant decrease in the serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, and lactic dehydrogenase and a significant increase in the tissue level of superoxide dismutase and glutathione; furthermore, it induced a significant decrease in malondialdehyde levels and improvement in histopathological changes in the liver tissues, confirming the potential hepatoprotective effects of the combination therapy on MTX-induced liver injury. To conclude, MTX-induced hepatotoxicity is mediated by induction of oxidative stress as evident by increased lipid peroxidation and reduction of antioxidant enzyme activity. Pretreatment with VC, CUR or their combination reduces the MTX-induced hepatotoxicity by antioxidant and anti-inflammatory effects. However, the combined effect of VC and CUR provided a synergistic hepatoprotective effect that surpasses pretreatment with CUR alone but seems to be similar to that of VC 200 mg/kg/day. Therefore, VC and CUR combination or a large dose of VC could be effective against MTX-induced hepatotoxicity. In this regard, further studies are warranted to confirm the combined hepatoprotective effect of VC and CUR against MTX-induced hepatotoxicity.

Dapagliflozin improves steatohepatitis in diabetic rats via inhibition of oxidative stress and inflammation

Type-2 diabetes mellitus and NAFLD are considered as one of the greatest worldwide metabolic disorders with growing incidence. It was found that patients with T2DM have two-fold increase to develop NAFLD. Evidence that some antidiabetic agents improve NAFLD/NASH in patients with T2DM is evolving. However, there are no certain pharmacologic therapies. The current study aimed to investigate the underlying mechanisms for the hepatoprotective effect of dapagliflozin against steatohepatitis in diabetic rats. Type-2 diabetes was induced by HFD followed by a single dose of STZ (30 mg/kg I.P). Fifty rats were randomly divided into 5 groups: Group1; normal control, Group 2; diabetic control, Groups (3–5); diabetic rats received daily dapagliflozin (0.75, 1.5, 3 mg/kg, p.o.) respectively for 6 weeks. At the end of the experiment, blood glucose level and serum insulin were measured. Hepatic tissue homogenization was performed for measuring inflammatory and oxidative stress markers. In addition, histopathological investigation of the hepatic tissue was done. Diabetic rats exhibited remarkable increase in liver weight and liver enzymes, along with histopathological changes, significant elevation in MDA, IL-1 β, TGFβ levels and, NF-κB, alpha-SMA expressions. Dapagliflozin treatment decreased liver weight, liver enzymes, together with marked improvement in histopathological changes. Furthermore, dapagliflozin increased antioxidant enzymes, GSH levels. Interestingly, Dapagliflozin reduced IL-1 β, TGFβ levels and, NF-κB, alpha-SMA expressions. Present data show that dapagliflozin represent a viable approach to protect the liver against diabetes-encouraged steatohepatitis through inhibiting oxidative stress, inflammation and fibrosis progression thus conserving liver function.

Anti-cryptosporidial activity of Camellia sinensis (green tea extract) in experimentally infected immunocompromised mice

Cryptosporidium parvum, an Apicomplexan parasite, is an important cause of diarrheal disease, especially in immunodeficient hosts. Nevertheless, there is no entirely successful therapeutic agent against cryptosporidiosis to date. Hence, this study aims to test the potential prophylactic and therapeutic effect of Camellia sinensis (green tea extract) in dexamethasone immunosuppressed mice versus the nowadays used drug, Nitazoxanide (NTZ). Parasitological and molecular methods were used to characterize Cryptosporidium oocysts before infection. Fifty bred female Swiss Albino mice were divided into 5 groups; group I (GI)(GTP): immunosuppressed and prophylactically treated with green tea extract for 5 days prior to infection, group II (GII)(GTT): immunosuppressed, infected with Cryptosporidium parvum and treated with green tea extract, group III (GIII)(NT): immunosuppressed, infected and treated with NTZ, group IV (GIV)(PC): immunosuppressed and infected (Positive control), group V (GV)(NC): immunosuppressed and non-infected (Negative control). Furthermore, parasitological examination for oocysts in the stool, and histopathological examination for the small intestine and liver specimens were performed for the study groups. Cryptosporidium oocysts used for induction of infection proved to be Cryptosporidium parvum genotype 2. Moreover, a significant oocyst reduction in fecal samples correlated with an improvement of histopathological changes in the small intestinal and liver tissues in GI(GTP), GII (GTT) and GIII(NT) groups. Besides, the GII(GTT) group showed the best improvement in parasitological and histopathological parameters among the test groups. This study revealed that Camellia sinensis (green tea extract) has potential activity against cryptosporidiosis and could serve as a promising prophylactic and therapeutic anti-cryptosporidial agent.

Effect of Grape Seeds (Vitis vinifera L.) and Mandarin Peels (Citrus reticulate L.) Extracts on the Cardiotoxicity Induced by Cyclophosphamide in Rats

Aims: The current study was developed to investigate the influence of grape seeds (GS) and mandarin peels (MP) extracts as powerful antioxidants on the cardiotoxicity induced by cyclophosphamide (CP) in rats.&#x0D; Place of Study: Department of Biochemistry and Nutrition, Faculty of Women for Arts, Science and Education, Ain Shams University.&#x0D; Methodology: Sixty adult male Sprague-Dawley rats were divided into 6 groups. Group (1): Rats were received distilled water daily orally for 6 weeks and injected interperitoneally (i.p) with saline (0.9 %) (2.5 ml / kg BW) as single dose at the end of the sixth week of experiment. Group (2): Rats were received distilled water orally and injected with single dose of cyclophosphamide which dissolved in saline (200 mg/kg BW. i.p.) at the end of the sixth week of experiment. Groups (3 and 4): Rats were received grape seeds extracts low and high doses (150 and 300 mg /kg BW), respectively daily orally for 6 weeks then injected with cyclophosphamide as group 2. Groups (5 and 6): Rats were received mandarin peels extracts low and high doses (150 and 300 mg /kg BW), respectively daily orally for 6 weeks then injected with cyclophosphamide as group 2.&#x0D; Results: Our results documented that CP caused a significant increase in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALK-P), creatine kinase (CK-MB), lactate dehydrogenase (LDH), creatine kinase (CK) enzymes activity and serum malondialdehyde (MDA) level. While total antioxidant capacity level (TAC) showed a significant decrease. On the other hand cardiac catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities and cardiac β cell lymphoma (Bcl-2) level showed a significant decrease in CP group while cardiac p53, caspase-3 and DNA fragmentation levels showed a significant increase in CP intoxicated group. Also, some histopathological changes were observed in liver and heart tissues in CP group. Oral administration of GS and MP caused an ameliorative effect in oxidative and apoptotic biomarkers, liver and heart function enzymes activity with an improvement of histopathological changes in liver and heart tissues.&#x0D; Conclusion: Our data proved that the protective effect of grape seeds and mandarin peels in cyclophosphamide intoxicated group may be due to their antioxidant, anti-inflammatory and anti- apoptotic properties.

The possible protective role of Coenzyme Q10 on the testis of rats treated with cisplatin

Background: Cisplatin is an anti-cancer drug that is associated with testicular toxicity because of its induction of excessive reactive oxygen species. Coenzyme Q10 (CoQ10) has been found to express antioxidant and anti-inflammatory effects. Aim: This study aims to investigate if CoQ10 can counter the testicular tissue toxicity caused by cisplatin. Methods: Animals were weighed and randomly divided into four groups (n = 10/each). In group I (control group), rats were received 1% of Tween-80 through intraperitoneal (i.p.) injection for 15 days. Group II (CoQ10 group) was i.p. treated for 15 days with CoQ10 in 1% tween-80 at a dosage of 10mg/kg/day for 15 days. Rats in group III (Cisplatin group) were i.p. treated with a single i.p. injection of cisplatin at a dosage of 7mg/kg on the 5th day of the experiment. Group IV (CoQ10/cisplatin) were i.p. treated with CoQ10 at a dosage of 10mg/kg/day for 15 days and cisplatin at a dosage of 7mg/kg on the 5th day of the experiment. The weight and dimensions of the testes were measured. Biochemical measurements, as well as histological and immunohistochemical morphometric, were done. Results: CoQ10 diminished cisplatin-induced oxidative stress by reducing lipid peroxidation and nitric oxide levels and increasing the levels of antioxidant enzymes, including superoxide dismutase and glutathione dehydrogenase. Moreover, CoQ10 significantly decreased the inflammatory response to cisplatin administration by decreasing the proinflammatory mediator tumor necrosis factor-α and increasing the anti-inflammatory cytokine IL-10. Treatment with CoQ10 also induced significant improvement in histopathological changes in testes. Conclusion: CoQ10 could protect testes against cisplatin-induced injury.

Nephroprotective effect of Apium graveolens L. against Cisplatin-induced nephrotoxicity

BackgroundCisplatin is extensively used in treating cancers, and its primary side-effect is nephrotoxicity. It accumulates in proximal convoluted tubules where it promotes cellular damage by oxidative stress, apoptosis, and inflammation, etc. In Unani medicine, Tukhm-e-Karafs(Apium graveolens L.) (TK) is mentioned in the literature to manage various kidney ailments due to its diuretic and deobstruent activities. ObjectiveTo investigate the nephroprotective effects of powder of TK in Cisplatin-induced nephrotoxicity in an animal model and to validate the Unani claim of its nephroprotective action. Material and methodsIn curative protocol, cisplatin (5 mg/kg body weight i.p) was administered on day one and powder of TK (500 and 1000 mg/kg p.o.) from the sixth day onwards for ten days. TK (500 and 1000 mg/kg p.o.) was given for ten days and Cisplatin (5 mg/kg body weight i.p) on day 11 in the protective model. At the end of the study, all the animals were sacrificed, and renal biochemical parameters were determined. KIM-1 level was also investigated in the kidney homogenate in conjunction with histopathological inspection of kidney tissues. ResultsSignificant increase in serum creatinine and BUN, presence of mononuclear cell infiltration, tubular dilation and vacuolation in renal histopathology, and increased KIM-1 level confirmed the nephrotoxicity due to Cisplatin. TK's administration protects the kidney as suggested by the changes in biochemical renal function, decreased level of KIM-1, and improvement in histopathological changes. ConclusionThe result advocated that TK prevented renal injury and maintained normal renal function in both models. It may be due to improved clearance of Cisplatin from kidney tubules and reduction in reactive oxygen species (ROS) produced by the inflammatory response.

Preparation and Biological Evaluation of Silybin Liposomes for the Treatment of Liver Disorders

Aim: The aim of the present study was to develop silybin liposome by incorporating phosphatidyl choline &amp; cholesterol so as to increase its oral bioavailability and liver targeted enhanced hepatoprotection.&#x0D; Methodology: Thin film hydration technique was used for the development of liposomes by using phosphatidyl choline, cholesterol and drug. Liposomes were evaluated for vesicle size, zeta potential, PDI, encapsulation efficiency, surface morphology and in vitro drug release study. Further the optimized formulation was evaluated for APAP-induced alterations in liver and kidney function tests in rats and histopathological studies.&#x0D; Results: The results were promising with a sustained drug release of 80% within 20hrs, optimized vesicle size of 276nm and 89% encapsulation efficiency. The animal studies demonstrated superior hepatoprotective effect compared to silybin solution.&#x0D; Conclusion: The silybin liposomes showed better in-vitro release &amp; in-vivo hepatoprotection along with better animal activity &amp; improvement in histopathological changes as compared to silybin.