Multicentric reticulohistiocytosis: A diagnostic challenge.

Multicentric reticulohistiocytosis, also called as lipoid dermato-arthritis is a rare form of non-Langerhans cell histiocytosis characterised by nodular and papular skin lesions containing characteristic bizarre multinucleate giant cells with ground glass cytoplasm. The disease commonly involves the skin, mucosa, synovium, and internal organs with cutaneous nodules and progressive erosive arthritis being the most common presenting features. We report a case of a 61-year-old male presenting with multiple swellings over distal part of fingers for 6 years without involvement of joints. A diagnosis of multicentric histiocytosis was made based on typical histopathological features of sheets of histiocytes and multinucleate giant cells with ground glass eosinophilic cytoplasm. The disease has a low incidence and about 300 cases have been reported so far in literature. The present case is being reported as it is uncommon for the disease to present in absence of arthritis.

Effects of high glutamate concentrations on mitochondria of human neuroblastoma SH-SY5Y cells.

BACKGROUND: The excess amount of glutamate in neurons is associated with the excitotoxicity and neurodegenerative diseases. Glutamate induces neurotoxicity primarily by immense influx of Ca2+ arising from overstimulation of the NMDA subtype of glutamate receptors. The neuronal death induced by the overstimulation of glutamate receptors depends critically on a sustained increase in mitochondrial Ca2+ influx and impairment in mitochondrial functions. The mitochondrial impairment is an important contributor to the glutamate-induced neuronal toxicity and thus provides an important target for the intervention. The present study investigates the effects of high glutamate concentrations on mitochondrial functions. RESULTS: Here, we have shown that the higher concentration of glutamate treatment caused a significant elevation in the N-methyl-D-aspartate (NMDA) receptors expression and elevated the intra-mitochondrial calcium accumulation in SHSY5Y neuronal cells. As a result of an accumulation of intra-mitochondrial calcium, there is a concentration-dependent elevation in ROS in the mitochondria. Tyrosine nitration of several mitochondrial proteins was increased while the mitochondrial membrane potential was dissipated. Furthermore, glutamate treatments also resulted in mitochondrial membrane permeability transition. CONCLUSIONS: These findings suggest that treatment of high glutamate concentration causes impairment of mitochondrial functions by an increase in intra-mitochondrial calcium, ROS production, dissipation of mitochondrial membrane potential and mitochondrial permeability transition pore opening in human neuroblastoma SHSY5Y cells.

Salvage Using Polatuzumab Vedotin Based Therapy in Relapsed Refractory Large B-Cell Lymphomas: Early Experience from a Real-World Middle-Income Setting Using Named-Patient Compassionate Access Program.

Polatuzumab vedotin is a novel immunotherapy antibody-drug conjugate targeting CD79b. It has been used in relapsed/refractory (R/R) large B-cell lymphomas since its FDA approval in 2019. Presently, this drug is unaffordable or unavailable for patients in Lower-Middle Income Countries (LMIC) like India. This is a retrospective study of adult (> 18 years) patients with R/R large B-cell lymphoma failing two prior lines of therapy, who received Polatuzumab based salvage therapy on a compassionate or named-patient access program. Between May 2019 and April 2022, 10 patients received Polatuzumab vedotin, and 9 were evaluable. The most common regimen used was Polatuzumab-Bendamustine-Rituximab. Out of 43 infusions administered, the adverse event profile was manageable [One grade-2 infusion reaction, 4 patients developed grade 3-4 hematological toxicity and none had grade 3-4 non-hematological toxicities]. Ten infusions were administered in the day care service. After a median of 4.5 cycles (range 1-8), 4 patients achieved CR, 2 had partial response (PR), and 3 had progressive disease (PD). With a median follow up of 491 days (range 8-1048 days), four patients are alive (three in CR and one in PR), three patients have died and three patients were lost to follow up. Early real-world experience from a LMIC setting demonstrates feasibility and a favourable safety profile of Polatuzumab vedotin based approach, along with encouraging response rates in a subset of patients.

Water budgeting in conservation agriculture-based sub-surface drip irrigation in tropical maize using HYDRUS-2D in South Asia.

In water scarce regions of South Asia, diversification of rice with maize is being advocated towards sustainability of cereal-based cropping systems. Adoption of innovative agronomic management practices, i.e., conservation agriculture (CA) and sub-surface drip irrigation (SSDI) are considered as key strategies for much needed interventions to address the challenges of water scarcity under projected climate change. Benefits from CA and SSDI concerning water economy are well-established, however, information about their complementarity and water budgeting in cereal-based systems are lacking. A field study was conducted with process-based model (HYDRUS-2D) to understand water transport, root water uptake and components of soil water balance in maize grown in rotation with wheat after five years of continuous adoption of conservation agriculture. In this study, altogether eight treatments comprising of 6 CA+ treatments (CA coupled with SSDI); permanent beds using sub-surface drip (PB-SSD) with (WR) and without (WOR) crop residue at different N rates, 0, 120 and 150 kg N ha-1 were compared with CA (PB using furrow irrigation-FI with crop residue-120 kg N ha-1) and conventional tillage practices (CT) (CT using FI without crop residue-120 kg N ha-1). Results showed that the model could simulate the daily changes in profile soil water content with reasonable accuracy in all the treatments. Simulated soil water balance indicated higher cumulative root water uptake (CRWU), lower cumulative evaporation (CE) and higher soil water retention in CA+ (PB-SSD+ crop residue at 150 and 120 kg N ha-1) than CA and CT plots. Hydrus-2D model efficiency > 0, RMSE between 0.009-0.026 and R2 value between 0.80-0.92 at P < 0.01 indicates that the model is performing efficiently. The mean evaporation from CA+ treatments was 10 and 36% less than CA and CT treatments, respectively. On average, CRWU under CA+ treatments were 14-48% higher than FI treatments. The mean cumulative deep drainage in CA+ plots was 80-100 mm less than CA and CT plots. In CA+ based plots significantly higher biomass production and radiation use efficiency were observed with reduced water use than CA and CT. Therefore, the study justifies the water-saving nature of CA+, while maintaining higher productivity and meeting the transpiration demand of crops and halting unnecessary evaporation and deep drainage losses.

Critical evaluation of functional aspects of evaporation barriers through environmental and economics lens for evaporation suppression - A review on milestones from improved technologies.

Climate change models predict an increase in rainfall variability, leading to floods and drought events, hence intensifying the need for reservoirs. However, up to 50% of reservoirs' capacity is lost by evaporation, affecting their function of ensuring water availability and stability. Over decades biological, chemical and physical barriers "covers" were developed for inhibiting evaporation. Such barrier's efficiency and applicability are still a matter of discussion, given their economic efficiency, environmental consequences, and operational difficulties are accounted for. In this review, we discussed the efficiency, applicability, and environmental suitability of these covers. Compared to the physical covers, the chemical and biological solutions tend to be less efficient. However, the use of physical covers is multidisciplinary, involving climate, material, and hydrological sciences, and are more efficient. Among the physical covers, the use of suspended covers and free-floating elements decreases evaporation to the tune of 85 and 80.0%, respectively. However, the economic efficiency of free-floating elements remains an open question since all studies overlooked their water footprint (water used in the manufacturing process of these covers), which was found to be very high. The use of these covers decreases heat storage, gas exchange rate, and light availability that could adversely influence dissolved oxygen, water quality, aquatic organisms, and the water ecosystem's function. These ecological consequences have not yet been investigated. The exception is the suspended covers, which have had determinate effects on dissolved oxygen and algae growth. Due to light weight, floating elements' operation is unstable and vulnerable to move due to wind effects. Therefore, such covers must be engineered to increase their stability. Free-floating elements could provide a visible and scalable solution to evaporation suppression when considering their economic visibility, environmental effects, and stability against wind and wave effects under the field conditions. However, these covers can be viable only when water availability is the limiting factor in crop production. We found that studies at reservoir scale are highly limited, therefore, investigations at reservoirs' scale emphasizing ecological aspects, cover stability and cost efficiency, are urgently needed.

Energy auditing and carbon footprint under long-term conservation agriculture-based intensive maize systems with diverse inorganic nitrogen management options.

A greater energy grant in diesel-fed machinery driven farming substantiate the higher GHGs emission along with improper input (fertilizer, pesticide and irrigation) use and intensive soil management. Practicing conservation tillage, residue retention and diversified crop rotations were advocated because of their multiple benefits. Hence we explored the energy requirement and carbon footprint of conservation agriculture (CA) based maize production systems. Coated N fertilizer [sulphur coated urea (SCU) and neem coated urea (NCU)] were compared with unfertilized and uncoated prilled urea (PU) in the scenario of with and without residue retention on permanent beds (PB) under diversified maize systems [MMuMb, maize-mustard-mungbean and MWMb, maize-wheat-mungbean] in search of a sustainable and energy efficient production system with lesser C-footprint. Results of the 4-year study showed that crops planted on permanent bed with crop residue (PB+R) registered 11.7% increase in system productivity compared to PB without residue (PB-R). N management through Neem coated urea (NCU) recorded 2.3 and 10.9% higher system productivity compared with non-coated prilled urea plot under PB-R and PB+R, respectively. MMuMb was marginally superior than MWMb system in terms of cropping sequence yield, profitability, and energy and carbon use efficiency. Crop residue retention in zero tilled PB increased cost of cultivation by 125 and 147 USD/ha in MMuMb and MWMb systems, respectively. The quantified carbon footprint value was higher in MWMb system. In CA-based practices, crop residues management contributed the highest energy input (61.5-68.4%) followed by fertilizer application (17-20%). Among N management practices, neem coated urea (NCU) significantly improved system productivity and profitability in all the residue applied plots compared to un-fertilized and prilled urea (PU) applied plots. Similarly, higher energy output was also observed in NCU treated plots. However, carbon footprint value was higher in PU (268-285 CO2-e kg/Mg) plots than NCU (259-264 CO2-e kg/Mg) treated plots. Thus, the study supports and recommends that the CA-based MMuMb system with efficient N management through NCU is an environmentally safe, clean and energy efficient one, hence can reduce carbon footprint, will ensure food security and will mitigate climate change.

Long-term impact of conservation agriculture and diversified maize rotations on carbon pools and stocks, mineral nitrogen fractions and nitrous oxide fluxes in inceptisol of India.

Given the increasing scarcity of production resources such as water, energy and labour coupled with growing climatic risks, maize-based production systems could be potential alternatives to intensive rice-wheat (RW) rotation in western Indo-Gangetic Plains (IGP). Conservation agriculture (CA) in maize systems has been widely promoted for minimizing soil degradation and ensuring sustainability under emerging climate change scenario. Such practices are also believed to provide mitigation co-benefits through reduced GHG emission and increased soil carbon sequestration. However, the combined effects of diversified crop rotations and CA-based management on GHG mitigation potential and other co-benefits are generally over looked and hence warrant greater attention. A field trial was conducted for 5-years to assess the changes in soil organic carbon fractions, mineral-N, N2O emission and global warming potential (GWP) of maize-based production systems under different tillage & crop establishment methods. Four diversified cropping systems i.e. maize-wheat-mungbean (MWMb), maize-chickpea-Sesbania (MCS), maize-mustard-mungbean (MMuMb) and maize-maize-Sesbania (MMS) were factorially combined with three tillage & crop establishment methods i.e. zero tilled permanent beds (PB), zero-tillage flat (ZT) and conventional tillage (CT) in a split-plot design. After 5-years of continued experimentation, we recorded that across the soil depths, SOC content, its pools and mineral-N fractions were greatly affected by tillage & crop establishment methods and cropping systems. ZT and PB increased SOC stock (0-30 cm depth) by 7.22-7.23 Mg C ha-1 whereas CT system increased it only by 0.88 Mg C ha-1as compared to initial value. Several researchers reported that SOC & mineral-N fraction contents in the top 30 cm soil depth are correlated with N2O-N emission. In our study, global warming potential (GWP) under CT system was higher by 18.1 and 17.4%, compared to CA-based ZT and PB, respectively. Among various maize systems, GWP of MMS were higher by 11.2, 6.7 and 6.6%, compared that of MWMb (1212 kg CO2-eq. ha-1), MCS (1274 kg CO2-eq. ha-1) and MMuMb (1275 kg CO2-eq. ha-1), respectively. The results of our study suggest that CA and diversified crop rotations should be promoted in north-western IGP and other similar agro-ecologies across the globe for ensuring food security, restoration of soil health and climate change mitigation, the key sustainable development goals (SDGs).

Synaptosomal and mitochondrial oxidative damage followed by behavioral impairments in streptozotocin induced diabetes mellitus: restoration by Malvastrum tricuspidatum.

Synaptosomal and mitochondrial impairments in the brain of diabetic individual manifest metabolic risk factors that most likely affect the brain functions. Diabetes is associated with the structural and functional alterations of the brain and neuronal loss leading to cognitive and other behavioral impairments, thus reducing the quality of life. The biochemical mechanisms underlying the diabetes-associated behavioral decline are poorly understood. In the present study, we examined the effects of hyperglycemia on the oxidative stress and behavioral functions in streptozotocin-induced diabetic mice. Our results showed the increase in oxidative stress in synaptosomes and brain mitochondria marked by an increase in lipid peroxidation and protein carbonyl content and decline in reduced glutathione in mice treated with streptozotocin. The oxidative damage in synaptosomes and brain mitochondria further caused impairment in locomotor and memory behavioral functions. Furthermore, we examined the protective effects of plant extract derived from Malvastrum tricuspidatum against STZ induced oxidative stress and behavioural impairments. For the first time we showed that this plant extract attenuate synaptosomal and mitochondrial oxidative stress and behavioral impairments in mice treated with streptozotocin. We suggest that streptozotocin caused impairments in synaptosomes and brain mitochondria and altered behavioral functions via increase in the oxidative stress and decrease in the antioxidant defense system. These impairments in synaptosomes and brain mitochondria and alterations in behavioral functions are significantly prevented by supplementation of Malvastrum tricuspidatum extract.

Increase in oxidative stress and mitochondrial impairment in hypothalamus of streptozotocin treated diabetic rat: Antioxidative effect of Withania somnifera.

Hypothalamus, the primary brain region for glucose sensing, is severely affected by oxidative stress in diabetes mellitus. Oxidative stress in this region of brain may cause severe impairment in neuronal metabolic functions. Mitochondria are prominent targets of oxidative stress and the combination of increased oxidative stress and mitochondrial dysfunctions may further decline hypothalamic neuronal functions. In the present study we examined the oxidative damage response, antioxidative responses and mitochondrial membrane permeability transition in hypothalamus of streptozotocin-treated diabetic rats. Our results show that streptozotocin significantly increases hypothalamic lipid peroxidation, protein carbonyl content while glutathione peroxidase and reduced glutathione were declined. Mitochondrial impairment marked by an increase in mitochondrial membrane permeabilization was seen following streptozotocin treatment in the hypothalamus. The oral administration of Withania somnifera root extract stabilized mitochondrial functions and prevented oxidative damage in the hypothalamus of diabetic rat. These findings suggest an increase in the oxidative stress and decline in antioxidative responses in the hypothalamus of streptozotocin treated diabetic rats. Withania somnifera root extract was found useful in reducing oxidative stress and mitochondrial impairment in hypothalamus of diabetic rat.

Efficiency of mitochondrially targeted gallic acid in reducing brain mitochondrial oxidative damage.

Oxidative stress is associated with mitochondrial impairments. Supplying mitochondria with potent antioxidants can reduce oxidative stress­induced mitochondrial impairment. Gallic acid can be used to reduce oxidative burden in mitochondria. In order to increase the bioavailability of gallic acid inside the mitochondria we synthesized mitochondrially targeted gallic acid and explored its preventive effects against sodium nitroprusside induced oxidative stress in isolated mitochondria. Our observations revealed an increase in oxidative stress,decrease in reduced glutathione in mitochondria and increase in the mitochondrial permeability pore transition due to sodium nitroprusside treatment. Pre­treatment of gallic acid and mitochondrially targeted gallic acid to sodium nitroprusside treated mitochondria not only significantly reduced the oxidative stress but also prevented mitochondrial permeability pore transition to a significant difference. Mitochondrially targeted gallic acid was found more effective in reducing oxidative stress and mitochondrial permeability pore transition than gallic acid. We conclude that mitochondrially targeted gallic acid can be used for preventing mitochondrial impairment caused by oxidative stress.

An international study of intrachromosomal amplification of chromosome 21 (iAMP21): cytogenetic characterization and outcome.

Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL). To date, fluorescence in situ hybridisation (FISH), with probes specific for the RUNX1 gene, provides the only reliable detection method (five or more RUNX1 signals per cell). Patients with iAMP21 are older (median age 9 years) with a low white cell count. Previously, we demonstrated a high relapse risk when these patients were treated as standard risk. Recent studies have shown improved outcome on intensive therapy. In view of these treatment implications, accurate identification is essential. Here we have studied the cytogenetics and outcome of 530 iAMP21 patients that highlighted the association of specific secondary chromosomal and genetic changes with iAMP21 to assist in diagnosis, including the gain of chromosome X, loss or deletion of chromosome 7, ETV6 and RB1 deletions. These iAMP21 patients when treated as high risk showed the same improved outcome as those in trial-based studies regardless of the backbone chemotherapy regimen given. This study reinforces the importance of intensified treatment to reduce the risk of relapse in iAMP21 patients. This now well-defined patient subgroup should be recognised by World Health Organisation (WHO) as a distinct entity of BCP-ALL.

Evo-devo of the germline and somatic gonad in nematodes.

Due to recent progress in the development of genetic tools, nematodes have become excellent models to address the mechanistic basis of evolution of development. The gonad is one of the most variable structures in nematodes, reflecting the diverse modes of reproduction and lifestyle in this phylum. During larval development, the gonad primordium has a key role in organizing the neighboring tissues. Therefore, changes in the development of the gonad do not only influence the evolution of its morphology but also the overall body plan of the nematode. Here, we review recent progress on the evolution of development of the germline and somatic gonad in nematodes.

Curcumin reduces oxidative damage by increasing reduced glutathione and preventing membrane permeability transition in isolated brain mitochondria.

Mitochondria are critical regulators of energy metabolism and programmed cell death pathways. Mitochondria are also the major site for the production of reactive oxygen species which make this organelle more susceptible to oxidative damage and impairments of mitochondrial functions. Antioxidants have been of limited therapeutic success to ameliorate the toxic effects of oxidative stress in mitochondria. One reason may be the inability of mitochondria to selectively take up antioxidants. In the present study we synthesized mitochondrially targeted curcumin with an aim of delivering this polyphenolic compound to isolated mitochondria. Our observations show the strong anti-oxidative effects of curcumin and mitochondrially targeted curcumin against the lipid peroxidation, protein carbonylation and mitochondrial permeability transition induced by tert-butylhydroperoxide. Both curcumin and mitochondrially targeted curcumin significantly enhanced endogenous reduced glutathione level in the mitochondria thus preserving mitochondrial defense system against oxidative stress. We concluded that curcumin and mitochondrially targeted curcumin protected mitochondria against tert-butylhydroperoxide by lowering the oxidative damage, increasing the availability of endogenous reduced glutathione and preserving the mitochondrial integrity. Importantly, mitochondrially targeted curcumin was found most effective in ameliorating oxidative stress and preserving mitochondrial integrity than curcumin.

Statins lower calcium-induced oxidative stress in isolated mitochondria.

Statins are widely used cholesterol-lowering agents that exert cholesterol-independent effects including antioxidative. The present study delineates the effects of statins, atorvastatin, and simvastatin on oxidative stress and functions of mitochondria that are the primary cellular sources of oxidative stress. In isolated rat liver mitochondria, both the statins prevented calcium-induced cytochrome c release, lipid peroxidation, and opening of the mitochondrial membrane permeability transition (MPT). Both the statins decreased the activity of mitochondrial nitric oxide synthase (mtNOS), lowered the intramitochondrial ionized calcium, and increased the mitochondrial transmembrane potential. Our findings suggest that statins lower intramitochondrial ionized calcium that decreases mtNOS activity, lowers oxidative stress, prevents MPT opening, and prevents the release of cytochrome c from the mitochondria. These results provide a novel framework for understanding the antioxidative properties of statins and their effects on mitochondrial functions.

Dietary restriction lowers endogenous levels of oxidative stress in different brain regions of adult mice.

Increase in the cellular burden of oxidative stress is critically involved in various pathological manifestations of aging, including age-related neurological disorders. Dietary restriction can lower reactive oxygen species formation, and thereby lower oxidative damage in the brain. The brain consists of a diverse group of neurons with varying functions. However, attenuating role of dietary restriction on oxidative stress in different regions of brain is not well known. In the present study we demonstrated that by restricting diet intake for a period of six months, mice lowered the endogenous levels of oxidative stress markedly by decreasing lipid peroxidation and protein carbonyl contents in cerebral cortex, hippocampus and striatum regions of the brain. Based on these results we suggest that dietary restriction can significantly reduce oxidative stress in various regions of the brain by virtue of lowering endogenous levels of reactive oxygen species, which might prove beneficial for preserving normal brain function with age.

Mitochondrial association of alpha-synuclein causes oxidative stress.

Alpha-synuclein is a neuron-specific protein that contributes to the pathology of Parkinson's disease via mitochondria-related mechanisms. The present study investigated possible interaction of alpha-synuclein with mitochondria and consequences of such interaction. Using SHSY cells overexpressing alpha-synuclein A53T mutant or wild-type, as well as isolated rat brain mitochondria, the present study shows that alpha-synuclein localizes at the mitochondrial membrane. In both SHSY cells and isolated mitochondria, interaction of alpha-synuclein with mitochondria causes release of cytochrome c, increase of mitochondrial calcium and nitric oxide, and oxidative modification of mitochondrial components. These findings suggest a pivotal role for mitochondria in oxidative stress and apoptosis induced by alpha-synuclein.

Alzheimer's disease pathogenesis and therapeutic interventions.

Alzheimer's disease (AD) is a neurodegenerative disorder of the central nervous system associated with progressive cognitive and memory loss. Molecular hallmarks of the disease are characterized by extracellular deposition of the amyloid beta peptide (Abeta) in senile plaques, the appearance of intracellular neurofibrillary tangles (NFT), cholinergic deficit, extensive neuronal loss and synaptic changes in the cerebral cortex and hippocampus and other areas of brain essential for cognitive and memory functions. Abeta deposition causes neuronal death via a number of possible mechanisms including oxidative stress, excitotoxicity, energy depletion, inflammation and apoptosis. Despite their multifactorial etiopathogenesis, genetics plays a primary role in progression of disease. To date genetic studies have revealed four genes that may be linked to autosomal dominant or familial early onset AD (FAD). These four genes include: amyloid precursor protein (APP), presenilin 1 (PS1), presenilin 2 (PS2) and apolipoprotein E (ApoE). Plaques are formed mostly from the deposition of Abeta, a peptide derived from APP. The main factors responsible for Abeta formation are mutation of APP or PS1 and PS2 genes or ApoE gene. All mutations associated with APP and PS proteins can lead to an increase in the production of Abeta peptides, specifically the more amyloidogenic form, Abeta42. In addition to genetic influences on amyloid plaque and intracellular tangle formation, environmental factors (e.g., cytokines, neurotoxins, etc.) may also play important role in the development and progression of AD. A direct understanding of the molecular mechanism of protein aggregation and its effects on neuronal cell death could open new therapeutic approaches. Some of the therapeutic approaches that have progressed to the clinical arena are the use of acetylcholinesterase inhibitors, nerve growth factors, nonsteroidal inflammatory drugs, estrogen and the compounds such as antioxidants, neuronal calcium channel blockers or antiapoptotic agents. Inhibition of secretase activity and blocking the formation of beta-amyloid oligomers and fibrils which may inhibit fibrilization and fibrilization-dependent neurotoxicity are the most promising therapeutic strategy against the accumulation of beta-amyloid fibrils associated with AD. Furthermore, development of immunotherapy could be an evolving promising therapeutic approach for the treatment of AD.

Susceptibility of hippocampus and cerebral cortex to oxidative damage in streptozotocin treated mice: prevention by extracts of Withania somnifera and Aloe vera.

Diabetes mellitus is reported to impair the memory function in experimental animals. Since the mammalian hippocampus and cerebral cortex play a pivotal role in a diverse set of cognitive functions, such as novelty detection and memory, we examined the vulnerability of cortex and hippocampus regions of the brain to oxidative damage in streptozotocin (STZ) diabetic mice. We next examined the attenuating effect of extracts of Withania somnifera and Aloe vera on prevention of hippocampal and cortical cell degenerations. Doses of both plant extracts given to experimental animals were based on the evaluation of their total antioxidant activity and also their potency to reduce Fe(3+). We assayed lipid peroxidation (LPO) and protein carbonyl (PC) in both regions of the brain and observed the changes in memory and motor behavioral functions in diabetic and control mice. The results showed a significant (P < 0.05) increase in LPO and PC in hippocampus and cortical regions of STZ diabetic mice. We also found a significant impairment in both motor and memory behavioral functions in diabetic mice. However, when diabetic mice were supplemented with the extracts of Withania somnifera and Aloe vera, the oxidative damage in both brain regions was reduced as marked by a significant (p < 0.05) declines in both LPO and PC. The combination of extracts of Withania somnifera and Aloe vera was more effective in reducing oxidative damage in brain regions than the supplementation of single plant extract. The combination also lowered the blood glucose level in comparison to STZ diabetic mice. Memory impairment and motor dysfunction were also improved by the plant extracts supplementation. We conclude that impairments in the hippocampus and cortex in STZ diabetic mice are associated with an increased free radical mediated oxidative damage and that the supplementation of plant extracts showed preventive effects in attenuating oxidative damage in both brain regions possibly via antioxidative mechanisms.

Experimental excitotoxicity provokes oxidative damage in mice brain and attenuation by extract of Asparagus racemosus.

Excitotoxicity and oxidative stress are the major mechanisms of neuronal cell death in neurodegenerative disorders that occurs in both Alzheimer's and Parkinson's diseases. Reactive oxygen species (ROS) that are generated extracellularly and intracellularly by various mechanisms are among the major risk factors that initiate and promote neurodegeneration.Therefore, it is important to find the compound which retard or reverse the neuronal injury. We designed this study to investigate the potential of extract of Asparagus racemosus (AR) against kainic acid (KA)-induced hippocampal and striatal neuronal damage. The dose of AR extract given to experimental animals was based on the evaluation of its total antioxidant activity. Extract of AR displayed potent reductant of Fe(3+). The excitotoxic lesion in brain was produced by intra-hippocampal and intra-striatal injections of kainic acid (KA; 0.25 microg in a volume of 0.5 microl) to ketamine and xylazine (200 and 2 mg/kg b.w. respectively) anesthetized mice. The results showed impairment of hippocampus and striatal regions of brain after KA injection marked by an increase in lipid peroxidation and protein carbonyl content and decline in glutathione peroxidase (GPx) activity and reduced glutathione (GSH) content. The AR extract supplemented mice displayed an improvement in GPx activity and GSH content and reduction in membranal lipid peroxidation and protein carbonyl. We show that the minimizing effect of AR extract on oxidative damage in addition to the elevation of GPx activity and GSH content could eventually result in protective effect on the KA-induced excitotoxicity.