Morphological alteration in mitochondria following diclofenac and ibuprofen administration.

This study was conducted to identify and to compare the mitochondrial morphological alterations in livers of rats treated with various doses of diclofenac and ibuprofen. Hundred and forty-four male Sprague Dawley rats were dosed with 3, 5 and 10 mg kg-1 diclofenac and ibuprofen in saline via intraperitoneal injection for 15 days. The control group was administered with saline in a similar manner. Four rats were euthanised every 3 days until day 15. While 200 mg kg-1 diclofenac and ibuprofen-treated rats (n = 4) were euthanized 10 h post-treatment. The livers were removed, cleaned and a section across the right lobe was taken and fixed in 4% (v/v) glutaraldehyde for electron microscopy analysis and the remaining samples were kept at -80°C for Western blot analysis. Five milligram per kilogram and 10 mg kg-1 diclofenac-administered rats for 15 days revealed the presence of enlarged mitochondria, irregular and ruptured mitochondrial membranes. While rats administered with 10 mg kg-1 ibuprofen also showed the presence of mitochondria with irregular membrane structure and ruptured membranes. Western blotting analysis of mitochondrial fractions revealed the expression of cytochrome c in all samples and complete absence of cytochrome c expression in the cytosolic fraction of all samples after day 15. Analysis in 200 mg kg -1 diclofenac and ibuprofen-treated groups, revealed expression of cytochrome c in both mitochondrial and cytosolic fractions. This observation indicates that both diclofenac and ibuprofen may alter the morphology of mitochondria, leading to cytochrome c release into the cytosol. Further studies needs to be conducted to investigate on the activity of the mitochondria following both treatments

Moringa oleifera enhances liver antioxidant status via elevation of antioxidant enzymes activity and counteracts paracetamol-induced hepatotoxicity.

This study investigated the role of antioxidant enzyme system following crude hydroethanolic extract of Moringa oleifera leaves (MO) in acute paracetamol (PCM) induced hepatotoxicity. Hydroethanolic extract (80%) of MO (200 mg/kg and 800 mg/kg; p.o) was pre-administered before a single oral dose of 3 g/kg PCM intoxication to male Sprague-Dawley rats. Pre-treatment of the extract was found to have reduced lipid peroxidation level when compared to the group treated with PCM only. The level of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR) was restored to near normal in groups that were pre-treated with MO. Histopathological studies have further confirmed the hepatoprotective activity of MO compared to group treated with PCM only. The results obtained were comparable to silymarin (200 mg/kg; p.o). The MO extract was found to have significantly protected the liver against toxicity following PCM intoxication by enhancing the level of antioxidant enzyme activity

Targeting energy metabolism to eliminate cancer cells

Adaptive metabolic responses toward a low oxygen environment are essential to maintain rapid proliferation and are relevant for tumorigenesis. Reprogramming of core metabolism in tumors confers a selective growth advantage such as the ability to evade apoptosis and/or enhance cell proliferation and promotes tumor growth and progression. One of the mechanisms that contributes to tumor growth is the impairment of cancer cell metabolism. In this review, we outline the small-molecule inhibitors identified over the past decade in targeting cancer cell metabolism and the usage of some of these molecules in clinical trials

Hepatoprotective and antioxidant action of Moringa oleifera lam. againsts acetaminophen induced hepatoxicity in rats.

This study is conducted to investigate the possible hepatoprotective action of Moringa oleifera Lam. (MO), a high value medicinal plant against a single high dose of APAP induced hepatotoxicity. Male Sprague Dawley rats were dosed with APAP (3000 mg kg-1 body weight; p.o.) to induce hepatocellular damage. In rats that were pretreated with MO (200 and 800 mg kg-1, p.o.) for 14 days prior to APAP treatment there was a reduction of liver enzymes (ALT, AST and ALP) and also the restoration of glutathione level. The biochemical results showed parallel finding with the histopathological analysis in which liver sections obtained from rats pretreated with MO, the damage was blocked. Intriguingly, MO alone has significantly elevated the level glutathione compared to the control group. The findings has suggested that Moringa oleifera Lam. is a promising product in protecting the liver against APAP induced liver injury via the restoration and elevation of glutathione level in the liver

Regenerative potential of secretome from dental stem cells: a systematic review of preclinical studies

Injury to tissues is a major clinical challenge due to the limited regenerative capacity of endogenous cells. Stem cell therapy is evolving rapidly as an alternative for tissue regeneration. However, increasing evidence suggests that the regenerative ability of stem cells is mainly mediated by paracrine actions of secretome that are generally secreted by the cells. We aimed to systematically evaluate the efficacy of dental stem cell (DSC)-conditioned medium in in vivo animal models of various tissue defects. A total of 15 eligible studies was included by searching Pubmed, Scopus and Medline databases up to August 2017. The risk of bias was assessed using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias tool. Of 15 studies, seven reported the therapeutic benefit of the conditioned medium on neurological diseases and three reported on joint/bone-related defects. Two interventions were on liver diseases, whereas the remaining three addressed myocardial infarction and reperfusion, lung injury and diabetes. Nine studies were performed using mouse models and the remaining six studies used rat models. The methodological quality of the studies was low, as most of the key elements required in reports of preclinical studies were not reported. The findings of this review suggested that conditioned medium from DSCs improved tissue regeneration and functional recovery. This current review strengthens the therapeutic benefit of cell-free product for tissue repair in animal models. A well-planned study utilizing validated outcome measures and long-term safety studies are required for possible translation to clinical trials

Nanotechnology in drug delivery: the need for more cell culture based studies in screening

Advances in biomedical science are leading to upsurge synthesis of nanodelivery systems for drug delivery. The systems were characterized by controlled, targeted and sustained drug delivery ability. Humans are the target of these systems, hence, animals whose systems resembles humans were used to predict outcome. Thus, increasing costs in money and time, plus ethical concerns over animal usage. However, with consideration and planning in experimental conditions, in vitro pharmacological studies of the nanodelivery can mimic the in vivo system. This can function as a simple method to investigate the effect of such materials without endangering animals especially at screening phase

Response of hepatic metabolizing enzymes and oxidative stress in orally administrated zerumbone against MIA-induced osteoarthritis in rats.

The main objective of this study was to elucidate the extent of hepatic oxidative stress following oral administration of zerumbone against monosodium iodoacetate induced Osteoarthritis (OA) in rats by monitoring microsomal cytochrome P450 and glutathione S-transferase enzymes as well as determination of oxidative stress biomarkers i.e., glutathione and malondialdehyde. Forty rats were randomly assigned into five groups. Rats in the first and second groups were treated with two different doses of zerumbone. Rats in the third group (positive control) were given celecoxib whereas the fourth group (negative control) was given corn oil. Rats of the fifth group were untreated not induced with OA and were used as a basal group. Results showed significant induction of cytochrome P450 and glutathione S-transferase and insignificant changes in both glutathione and lipid peroxidation levels in zerumbone treated groups compared to corn oil and basal groups. Levels of ALT and AST in zerumbone treated groups were comparable to the level in the basal group indicating absence of liver damage. Prostaglandin E2 level significantly reduced following zerumbone administration. Safety profile of zerumbone in this study, attract new investigation to explore its advantageous effect on using higher dosage regimen and/or longer duration against OA or other disease

Cytotoxic profiles of a nanodrug delivery based on 6-mercaptopurine-coated magnetite-peg nanoparticles towards leukemia (WEHI-3B) cell lines

A drug active, 6-mercaptopurine (MP) was coated on the surface of Fe3O4-PEG nanoparticles using co-precipitation method in order to form a new magnetic nanocomposite (FPEGMP). The physico-chemical properties of the nanocomposite were studied via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis and transmission electron microscopy. The resulting superparamagnetic nanocomposite has spherical shape with average particle size diameter of 11 nm. Thermal analyses and Fourier transform infrared (FTIR) spectroscopy revealed the formation of PEG-MP on the surface of iron oxide nanoparticles and the enhancement of the thermal stability of the nanocomposite compared to its counterpart, free 6-mercaptopurine. Release behavior of MP from FPEGMP nanocomposite was found to be sustained and governed by pseudo-second order kinetic. The maximum percentage release of MP from FPEGMP nanocomposite reached about 60% and 97% within approximately 92 and 72 hours when exposed to aqueous solutions at pH 7.4 and pH 4.8, respectively. Anti-cancer activity of the nanocomposite shows that the choice of coating material as well as the percentage of loading of the active agent could affect the cytotoxic activity of nanocomposite towards the mouse myelomonocytic leukemic cell line (WEHI-3B)

Moringa oleifera Lam prevents acetaminophen induced liver injury through restoration of glutathione level

Initiation of acetaminophen (APAP) toxicities is believed to be promoted by oxidative stress during the event of overdosage. The aim of the present study was to evaluate the hepatoprotective action of Moringa oleifera Lam (MO), an Asian plant of high medicinal value, against a single high dose of APAP. Groups of five male Sprague–Dawley rats were pre-administered with MO (200 and 800 mg/kg) prior to a single dose of APAP (3 g/kg body weight; p.o). Silymarin was used as an established hepatoprotective drug against APAP induced liver injury. The hepatoprotective activity of MO extract was observed following significant histopathological analysis and reduction of the level of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in groups pretreated with MO compared to those treated with APAP alone. Meanwhile, the level of glutathione (GSH) was found to be restored in MO-treated animals compared to the groups treated with APAP alone. These observations were comparable to the group pretreated with silymarin prior to APAP administration. Group that was treated with APAP alone exhibited high level of transaminases and ALP activities besides reduction in the GSH level. The histological hepatocellular deterioration was also evidenced. The results from the present study suggested that the leaves of MO can prevent hepatic injuries from APAP induced through preventing the decline of glutathione level

The histomorphological analysis of liver following administration of low doses of diclofenac and ibuprofen

This study was conducted to investigate and to compare liver perturbation following administration of low doses of diclofenac and ibuprofen to rats. Hundred and forty-four male Sprague Dawley rats were dosed with 3, 5 and 10 mg kg-1 diclofenac and ibuprofen in saline via intraperitoneal injection for 15 days. The control group was administered with saline in a similar manner. Four rats were euthanised every three days until day 15. Livers were removed, cleaned and a section across the right lobe was taken and fixed in 10% formalin for light microscopy and TUNEL assay. One-way ANOVA was used to analyse the data. p<0.05 was accepted as significant in this study. Three, 5 and 10 mg kg-1 diclofenac-treated groups and 5, 10 mg kg-1 ibuprofen administered groups showed significant changes compared to saline-treated group at day 15. The changes include presence of focal infiltration by neutrophils and lymphocytes and mild focal necrosis. In 5 and 10 mg kg-1 diclofenac administered groups and 10 mg kg-1 ibuprofen-treated group, apoptotic cells were seen around the perivenular regions (PV) only at day 15. However, not all the PVs were present with apoptotic cells. This study has shown that, diclofenac is probably more potent in inducing histomorphological changes at low doses. Both the drugs seem to exert time and dose dependent liver morphological alterations to the treated animals