Stroke is an increasingly prevalent clinical condition and second leading cause of death globally. The present study evaluated the therapeutic potential of Indian Ginseng, also known as Withania somnifera (WS), supplementation on middle cerebral artery occlusion (MCAO) induced mitochondrial dysfunctions in experimental model of ischemic stroke. Stroke was induced in animals by occluding the middle cerebral artery, followed by reperfusion injury. Ischemia reperfusion injury resulted in increased oxidative stress indicated by increased reactive oxygen species and protein carbonyl levels; compromised antioxidant system; in terms of reduced superoxide dismutase and catalase activity, along with reduction in GSH levels and the redox ratio, impaired mitochondrial functions and enhanced expression of apoptosis markers. Ischemia reperfusion injury induced mitochondrial dysfunctions in terms of (i) reduced activity of the mitochondrial respiratory chain enzymes, (ii) reduced histochemical staining of complex-II and IV, (iii) reduced in-gel activity of mitochondrial complex-I to V, (iv) mitochondrial structural changes in terms of increased mitochondrial swelling, reduced mitochondrial membrane potential and ultrastructural changes. Additionally, an increase in the activity of caspase-3 and caspase-9 was also observed, along with altered expression of apoptotic proteins Bcl-2 and Bax in MCAO animals. MCAO animals also showed significant impairment in cognitive functions assessed using Y maze test. WS pre-supplementation, on the other hand ameliorated MCAO induced oxidative stress, mitochondrial dysfunctions, apoptosis and cognitive impairments. The results show protective effect of WS pre-supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
3-Nitropropionic acid (3-NP) is an irreversible inhibitor of succinate dehydrogenase and induces neuropathological changes similar to those observed in Huntington's disease (HD). The objective of the present study was to investigate neuroprotective effect of mitochondrial modulators; alpha-lipoic acid (ALA) and acetyl-L-carnitine (ALCAR) on 3-NP-induced alterations in mitochondrial lipid composition, mitochondrial structure and memory functions. Experimental model of HD was developed by administering 3-NP at sub-chronic doses, twice daily for 17 days. The levels of conjugated dienes, cholesterol and glycolipids were significantly increased, whereas the levels of phospholipids (phosphatidylethanolamine, phosphatidylcholine, phosphatidylserine) including cardiolipin were significantly decreased in the mitochondria isolated from the striatum of 3-NP-treated animals. In addition, the difference in molecular composition of each phospholipid class was also evaluated using mass spectrometry. Mitochondria lipid from 3-NP-treated animals showed increased cholesterol to phospholipid ratio, suggesting decreased mitochondrial membrane fluidity. 3-NP administration also resulted in ultra-structural changes in mitochondria, accompanied by swelling as assessed by transmission electron microscopy. The 3-NP administered animals had impaired spatial memory evaluated using elevated plus maze test. However, combined supplementation with ALA + ALCAR for 21 days normalized mitochondrial lipid composition, improved mitochondrial structure and ameliorated memory impairments in 3-NP-treated animals, suggesting an imperative role of these two modulators in combination in the management of HD.
The present study was designed to evaluate the beneficial effects of Withania somnifera (WS) pre-supplementation on middle cerebral artery occlusion (MCAO) model of ischemic stroke. Ischemic stroke was induced in the rats by inserting intraluminal suture for 90 min, followed by reperfusion injury for 24 h. The animals were assessed for locomotor functions (by neurological deficit scores, narrow beam walk and rotarod test), cognitive and anxiety-like behavioural functions (by morris water maze and elevated plus maze test). MCAO animals showed significant impairment in locomotor and cognitive functions. Neurobehavioural changes were accompanied by decreased acetylcholinesterase activity, increased oxidative stress in terms of enhanced lipid peroxidation and lowered thiol levels in the MCAO animals. In addition, MCAO animals had cerebral infarcts and the presence of pycnotic nuclei. Single-photon emission computerized tomography (SPECT) of MCAO animals revealed a cerebral infarct as a hypoactive area. On the other hand, pre-supplementation with WS (300 mg/kg body weight) for 30 days to MCAO animals was effective in restoring the acetylcholinesterase activity, lipid peroxidation, thiols and attenuated MCAO induced behavioural deficits. WS significantly reduced the cerebral infarct volume and ameliorated histopathological alterations. Improved blood flow was observed in the SPECT images from the brain regions of ischemic rats pre-treated with WS. The results of the study showed a protective effect of WS supplementation in ischemic stroke and are suggestive of its potential application in stroke management.
The present study elucidated the protective potential of selenium following ¹³¹I-induced alterations in rat blood. Forty rats were segregated into 4 groups. Animals in Group I served as normal controls, Group II animals were injected with a single dose of 3.7 Mbq of ¹³¹I (carrier free), Group III animals were supplemented with selenium (1 ppm), and Group IV animals were given a combined treatment of selenium and ¹³¹I. ¹³¹I treatment of rats showed significant increases in total leukocyte counts (TLCs), lymphocytes, and neutrophils (monocytes and eosinophils were not recorded). These were significantly restored upon supplementation of selenium. Lipid peroxidase (LPO), glutathione peroxidase (GSH-PX), reduced glutathione (GSH), superoxide dismutase (SOD), and δ-aminolevulinic acid dehydratase (δ-ALAD) were found to be enhanced following ¹³¹I treatment. However, the levels of catalase were found to be decreased. Selenium administration to ¹³¹I-treated rats resulted in significant restoration of these enzyme activities. Scanning electron microscope (SEM) studies also revealed various surface deformities in erythrocytes after ¹³¹I treatment, which upon supplementation with selenium were significantly restored. In conclusion, selenium may prove to be an effective radioprotector following ¹³¹I treatment.
Viral infections are well known to pose a serious health threat if not treated on time, which is the current scenario of almost all nations of the world due to COVID19 pandemic. The disease believed to be originated from China in last December has killed >30,000 and infected around 550,000 worldwide in just a span of 3-4 months still poses a larger risk to the society due to unavailability of a potential drug or any other therapeutic intervention. However, the only treatment options available are the drugs prescribed in symptoms similar to those observed in COVID19 or by social distancing so as to halt the mode of human transmission from an infected person any further. Such a situation also highlights that, although we may have achieved scientific advancements in several other medical conditions but more efforts are warranted in near future to limit the spread of such pandemic outbreak. This review introduces the basic concept of COVID19, its epidemiology, diagnosis and management strategies to be followed till any therapeutic drug is made available over the counter.
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