Iron-Induced Oxidative Stress in Erythrocyte Membranes of Non-Insulin-Dependent Diabetic Nigerians

The presence of higher level of endogenous free radical reaction products in the erythrocyte ghost membrane (EGM) of Non-insulin-dependent diabetes mellitus (NIDDM) subjects compared with that of normal healthy controls has been demonstrated. The EGMs of NIDDM subjects were also shown to be more susceptible to exogenously generated oxidative stress than those of normal healthy individuals. The decreased level of reactive thiol groups in the EGM of NIDDM individuals supported this observation. We propose that the presence of significant levels of non-heme iron in the EGM of NIDDM subjects is an indication of the potential for iron-catalysed production of hydroxy and other toxic radicals which could cause continuous oxidative stress and tissue damage. Oxygen free radicals could therefore be responsible for most of the erythrocyte abnormalities associated with non-insulin-dependent diabetes and could indeed be intimately involved in the mechanism of tissue damage in diabetic complications

Reversal of Sodium Arsenite Inhibition of Rat Liver Microsomal Ca2+ Pumping ATPase by Vitamin C

Sodium arsenite (NaAsO2), at 10% of its median lethal dose, was administered to rats with and without vitamin C pretreatment. Liver microsomal fraction was isolated and the activity of Ca2+-ATPase was assayed. Sodium arsenite was found to inhibit the activity of the liver microsomal Ca2+-ATPase to 50% to that of control rats. The specific activity of the enzyme in rats administered sodium arsenite with vitamin C pretreatment was not significantly different from that of control rats

Methanol fraction of Calliandra portoricensis root bark activates caspases via alteration in mitochondrial viability in vivo

Introduction: Dysregulated apoptosis is associated with a number of disease conditions. Traditionally, Calliandra portoricensis is used in the management of prostate enlargement. This study investigates the in vivo effect of potent methanol fraction of C. portoricensis (MFCP) on mitochondrial permeability transition (mPT) pore, an important pharmacological target in treatment of various diseases, and examines the toxicities associated with its oral administration. Methods: Forty-two male Wistar strain rats (70-80 g) were divided into 6 groups of 7 animals each. Each group was orally administered 25, 50, 100, 200, 400 mg/kg MFCP and the control group received distilled water for 21 and 30 days, respectively. mPT, assay for serum enzymes and hematological parameters were assessed spectrophotometrically while activation of caspases 3 and 9 was done by ELISA technique. Histological assessment of vital organs (liver, kidney, prostate) was carried out according to standard procedures. Results: There were no significant effects on mPT pore at all doses administered after 21 days of oral administration. However, after 30 days of administration, MFCP induced mPT pore opening at doses 100 and 200 mg/kg with induction folds of 2.6 and 3.3, respectively while there was no induction of mPT pore opening at lower doses of 25 mg/kg and 50 mg/kg. Furthermore, significant (P < 0.05) increases in serum enzymes (ALT, AST) were observed at all doses administered when compared with control after 30 days of oral administration. Cell counts (Hb, PCV, RBC, WBC) were adversely affected at the highest dose (200 mg/kg) compared with control and other treated groups (25, 50 and 100 mg/kg) after 30 days of administration. Similarly, activation of caspases 9 and 3 were observed in rat liver homogenate at high doses of the fraction while histological evaluation showed degeneration and distortion of organs at the highest dose. Conclusion: MFCP contains phytochemicals that elicit the opening of the pore and induction of mitochondrial-mediated apoptosis. This would be relevant in treatment of degenerative diseases that results from down-regulation of apoptosis. However, caution should be exercised in using high doses of the plant

Distinct Metal Ion Requirements for the Phosphomonoesterase and Phosphodiesterase Activities of Calf Intestinal Alkaline Phosphatase

The roles of Mg2+ and Zn2+ ions in promoting phosphoryl transfer catalysed by alkaline phosphatase are yet to be fully characterised. We investigated the divalent metal ion requirements for the monoesterase and diesterase activities of calf intestinal alkaline phosphatase. The synergistic effect of Mg2+ and Zn2+ in promoting the hydrolysis of para-nitrophenyl phosphate (monoesterase reaction) by alkaline phosphatase is not observed in the hydrolysis of the diesterase substrate, bis-para-nitrophenyl phosphate. Indeed, the diesterase reaction is inhibited by concentrations of Mg2+ that were optimal for the monoesterase reaction. This study reveals that the substrate specificities of alkaline phosphatases and related bimetalloenzymes are subject to regulation by changes in the nature and availability of cofactors, and the different cofactor requirements of the monoesterase and diesterase reactions of mammalian alkaline phosphatases could have significance for the biological functions of the enzymes

Effect of Crude Methanol Extract of Heliotropium indicum on Certain Biochemical Parameters in Rats with Monosodium Glutamate-Induced Fibroids

Background: Uterine fibroids or uterine leiomyoma are the commonest non-cancerous tumor affecting mostly women of age between 30-45 years. Hormones such as estrogen and progesterone produced by the ovaries cause the regeneration of the uterine lining which may stimulate the growth of fibroids. It has been established that monosodium glutamate (MSG) (a commonly used food seasoning) induces fibroids by increasing the levels of cholesterol, estradiol and total protein. Heliotropium indicum has been indicated in folkloric medicine to be anti-tumoric. The effect of crude Methanol Extract of Heliotropium indicum (MEHI) on some biochemical parameters in MSG-induced fibroid was studied. Materials and Methods: Twenty-five female Wistar rats were divided into five study groups; A(Control), B(MEHI – 50mg/kg bdwt), C(MSG – 50mg/kg bdwt), D(MSG - 50mg/kg bdwt + MEHI - 50mg/kg bdwt) and E(MSG - 50mg/kg bdwt + MEHI - 100mg/kg bdwt). The administration was carried out through intraperitoneal injection for 10days. The animals were fasted for 24hours before sacrifice after which the blood was collected into appropriate sample bottles. The levels of progesterone, estradiol, cholesterol, liver enzymes, antioxidant and hematological parameters were estimated using standard procedures. Results: The results showed that the MEHI has an ameliorative effect on MSG-induced fibroid as seen in its ability to reduce elevated levels of cholesterol, progesterone and estradiol. Also the extract elevated the levels of liver enzymes and antioxidants. Although there was insignificant decrease in the levels of antioxidants, this might be because the extract competes with the antioxidants for active site. Also, the plant extract improved packed cell volume and thus, elicits its ability as co-treatment for anaemia. Lesions at histopathology of uterus exposed to MSG alone revealed striking lesions ranging from moderate diffuse cellular infiltrates and hyperplastic endometrial glands in uterine mucosa to degenerate and necrotizing endometrial mucosa with atrophy of glands, while the ovaries exhibited lesions ranging from obliteration of ovarian follicles to attenuation of germinal epithelium (diffuse oophoritis). On the other hand the inclusion of MEHI in MSG- fibroid induced rat led to acute endometritis, moderate diffuse endometritis and glandular hyperplasia (uterus), while lesions in the ovaries ranged slightly from follicular atresia, atrophy of the gonads to normal ovaries in a dose dependent manner.Conclusion: These findings showed that the plant extract can be used for the treatment of uterine fibroid and its use could lead to improved packed cell volume of the patient, antioxidants activities and regulation of female reproductive hormones. Also, MSG has high fibroid generation tendencies which could lead to destruction of ovaries and uterus when consumed incessantly, while MEHI, showed a great potential in ameliorating the effect of MSG on ovaries and uterus, hence, MEHI is ovariohysteric protective. Keywords: Uterine Fibroids, MSG, Heliotropiumindicum, PCV, Antioxidant

In vitro induction of rat liver mitochondrial membrane permeability transition pore opening by solvent extracts of Momordica charantia leaves

Alteration of mitochondrial functions such as permeability transition (PT), a process associated with the uncoupling of oxidative phosphorylation, has been found to play a vital role in the apoptotic process induced by certain anti-cancer agents. When triggered, PT facilitates the release of mitochondrial apoptogenic proteins which in turn activate the caspase cascade of apoptosis. Thus, this study investigated the in vitro effects of varying concentrations (0.2, 0.4, 0.6, 0.8 and 1.0 mg/ml) of different leaf extracts [Crude Water-Soluble Extract (CWSE), Decoction (DE) and Methanol Extract (ME)] of Momordica charantia (M. charantia), a purported anti-cancer plant of the family Cucurbitaceae on normal rat liver mitochondria. Opening of mitochondrial membrane permeability transition pore (MMPTP) was spectrophotometrically assayed under succinate-energized condition. Results obtained showed concentration-dependent and significant (P&lt;0.05) increases in the extents to which MMPTP opening was induced by the three extract types when compared with the control group. Inductions caused by CWSE and DE increased with increasing concentrations while those caused by ME decreased with increasing concentrations, giving the maximum induction at 1.0 mg/ml (8.1-fold increase) of CWSE and the least induction at 1.0 mg/ml (4.3-fold increase) of ME, respectively. Spermine, a reference inhibitor of MMPTP opening, reversed all observed openings. These results indicate that the tested leaf extracts of M. charantia are potent (CWSE being the most potent) MMPTP opening inducers and the pathway by which M. charantia causes apoptosis in cancer cells is probably mitochondrial-mediated (intrinsic).Keywords: Mitochondrial membrane permeability transition pore (MMPTP), Momordica charantia, Apoptosis, Spermine

Hepatoprotective Activity and Inhibitory Effect of Flavonoid -Rich Extract of Brysocarpus Coccineus Leaves on Mitochondrial Membrane Permeability Transition Pore

ABSTRAC

Glyphosate does not substitute for glycine in proteins of actively dividing mammalian cells

Glyphosate (N-phosphonomethyl glycine) and its commercial herbicide formulations have been shown to exert toxicity via various mechanisms. It has been asserted that glyphosate substitutes for glycine in polypeptide chains leading to protein misfolding and toxicity. However, as no direct evidence exists for glycine to glyphosate substitution in proteins, including in mammalian organisms, we tested this claim by conducting a proteomics analysis of MDA-MB-231 human breast cancer cells grown in the presence of 100 mg/L glyphosate for 6 days. Protein extracts from three treated and three untreated cell cultures were analysed as one TMT-6plex labelled sample, to highlight a specific pattern (+/+/+/−/−/−) of reporter intensities for peptides bearing true glyphosate treatment induced-post translational modifications as well as allowing an investigation of the total proteome

Regional and experiential differences in surgeon preference for the treatment of cervical facet injuries: a case study survey with the AO Spine Cervical Classification Validation Group

Purpose: The management of cervical facet dislocation injuries remains controversial. The main purpose of this investigation was to identify whether a surgeon’s geographic location or years in practice influences their preferred management of traumatic cervical facet dislocation injuries. Methods: A survey was sent to 272 AO Spine members across all geographic regions and with a variety of practice experience. The survey included clinical case scenarios of cervical facet dislocation injuries and asked responders to select preferences among various diagnostic and management options. Results: A total of 189 complete responses were received. Over 50% of responding surgeons in each region elected to initiate management of cervical facet dislocation injuries with an MRI, with 6 case exceptions. Overall, there was considerable agreement between American and European responders regarding management of these injuries, with only 3 cases exhibiting a significant difference. Additionally, results also exhibited considerable management agreement between those with ≤ 10 and &gt; 10&nbsp;years of practice experience, with only 2 case exceptions noted. Conclusion: More than half of responders, regardless of geographical location or practice experience, identified MRI as a screening imaging modality when managing cervical facet dislocation injuries, regardless of the status of the spinal cord and prior to any additional intervention. Additionally, a majority of surgeons would elect an anterior approach for the surgical management of these injuries. The study found overall agreement in management preferences of cervical facet dislocation injuries around the globe