Naringenin alleviates paraquat-induced dopaminergic neuronal loss in SH-SY5Y cells and a rat model of Parkinson's disease.

Parkinson's disease (PD), a common neurodegenerative disease is characterized by the progressive loss of dopaminergic neurons in the substantia nigra. The cause of dopaminergic loss in PD remains unknown for a long time, however, recent reports suggest oxidative stress plays a key role in the pathogenesis of PD. Paraquat (PQ), a widely used herbicide is an oxidative stress inducer that has been implicated as a potential risk factor for the development of PD. Flavonoids are naturally occurring polyphenolic compounds that display a variety of therapeutic properties against oxidative stress. Naringenin (NAR), a natural flavonoid, exhibits neuroprotection against PD-related pathology. However, studies on its neuroprotective role and the underlying mechanisms are scarce, therefore the present study explored the potential neuroprotective role of NAR in PQ-induced parkinsonism in SH-SY5Y cells and rat model. The effect of NAR on PQ-induced cellular toxicity was determined by measuring cell viability, oxidative stress, ATP levels and the same effect was determined by assessing behavioral, biochemical, immunohistochemical, qRT-PCR and Western blot in rat model. NAR treatment in SH-SY5Y cells resulted in increased cell viability, reduced oxidative stress, elevated mitochondrial membrane potential, and higher cellular ATP levels. In rats, NAR treatment resulted in significant neuroprotection against PQ-induced behavioral deficits, oxidative stress, mitochondrial dysfunction, and astrocytosis. NAR treatment significantly modulated PQ-induced mRNA expressions of DRD2, DAT, LRRK2, SNCA, ß-catenin, caspase-3, BDNF genes. NAR treatment increased TH protein expression and modulated its immunoreactivity in rat striatum. Also, GFAP decreased in response to NAR treatment. So, in the present study, NAR exhibits neuroprotection against PQ-induced neurotoxicity and neurodegeneration indicating its novel therapeutic potential against PD.

Pathophysiological implications of neuroinflammation mediated HPA axis dysregulation in the prognosis of cancer and depression.

Cancer patients are more likely to develop depressive symptoms and show a poor prognosis compared to the normal healthy individuals. Cancer occurrence and the anticancer treatments result in the pro-inflammatory cytokines-mediated inflammation, which dysregulates the HPA-axis activity that may result in depression-like behaviour. Conversely, depression causes the activation of the HPA-axis that results in the downstream release of endogenous glucocorticoids which may result in depressive signs and symptoms in some cancer patients. Depression may also result in non-adherence to treatment and increased mortality in cancer patients. In this review, we have focused on the role of neuroimmune axis and hyperactive HPA-axis in case of both cancer and depression. Therefore, therapeutics targeting the HPA-axis dysregulation could be effective in ameliorating symptoms of depression in cancer patients.

Piperine-Coated Gold Nanoparticles Alleviate Paraquat-Induced Neurotoxicity in Drosophila melanogaster.

Parkinson's disease (PD) is the most common progressive neurodegenerative disease known to impart bradykinesia leading to diverse metabolic complications. Currently, scarcity of effective drug candidates against this long-term devastating disorder poses a big therapeutic challenge. Here, we have synthesized biocompatible, polycrystalline, and uniform piperine-coated gold nanoparticles (AuNPspiperine) to specifically target paraquat-induced metabolic complications both in Drosophila melanogaster and SH-SY5Y cells. Our experimental evidence clearly revealed that AuNPspiperine can effectively reverse paraquat-induced lethal effects in both in vitro and in vivo model systems of PD. AuNPspiperine were found to suppress oxidative stress and mitochondrial dysfunction, leading to inhibition of apoptotic cell death in paraquat-treated flies. AuNPspiperine were also found to protect SH-SY5Y cells against paraquat-induced toxicity at the cellular level preferably by maintaining mitochondrial membrane potential. Both experimental and computational data point to the possible influence of AuNPspiperine in regulating the homeostasis of parkin and p53 which may turn out to be the key factors in reducing PD symptoms. The findings of this work may facilitate the development of piperine-based nanoformulations against PD.

Ropinirole silver nanocomposite attenuates neurodegeneration in the transgenic Drosophila melanogaster model of Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease due to the degeneration of dopaminergic neurons in substantia nigra pars compacta of the mid brain. The present study investigates the neuro-protective role of synthesized ropinirole silver nanocomposite (RPAgNC) in Drosophila model of PD. α-synuclein accumulation in the brain of flies (PD flies) leads to the damage of dopaminergic neurons, dopamine depletion, impaired muscular coordination, memory decline and increase in oxidative stress. Ingestion of the RPAgNC by Drosophila significantly prevented the neuronal degeneration compared to only ropinirole. The results confirm that the RPAgNC exerts more neuro-protective effect compared to dopamine agonist i.e. ropinirole as such drug in experimental PD flies. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.

A selective D2 dopamine receptor agonist alleviates depression through up-regulation of tyrosine hydroxylase and increased neurogenesis in hippocampus of the prenatally stressed rats.

Prenatal stress (PNS) has its negative impact on both the infant hippocampal neurogenesis and pregnancy outcomes in the neonates that serves as a risk factor for postnatal depression in adult offsprings. Therefore, main objectives of the present study were to evaluate the effect of maternal chronic unpredictable mild stress (CUMS) on behavioural changes, levels of oxidative stress, changes in selective developmental signaling genes and neurogenesis in the adult brain of Wistar rats and its reversal through a selective non-ergoline D2 type dopamine receptor (D2R) agonist Ropinirole (ROPI). Effects of ROPI treatment on CUMS induced adult rats offspring were measured by assessment of behavioural tests (sucrose preference test and forced swim test), biomarkers of oxidative stress, protein expression of tyrosine hydroxylase (TH), mRNA expression of SHH, GSK-3ß, ß-catenin, Notch, brain-derived neurotrophic factor (BDNF), Dopamine receptor 2 (Drd2) and bromodeoxyuridine (BrdU) cell proliferation assay. The oxidative stress, protein and mRNA expression were determined in the hippocampus and prefrontal cortex while the BrdU cell proliferation was observed in the hippocampus of rat brain. PNS induced changes resulted in depression validated by the depression-like behaviours, increased oxidative stress, decreased TH expression, altered expression of selective developmental genes, along with the reduced hippocampal neurogenesis and BDNF expression in the brain of adult offsprings. Chronic ROPI treatment reversed those effects and was equally effective like Imipramine (IMI) treatment. So, the present study suggested that ROPI can be used as an antidepressant drug for the treatment of depressive disorders.

A Synthetic Pro-Drug Peptide Reverses Amyloid-ß-Induced Toxicity in the Rat Model of Alzheimer's Disease.

BACKGROUND: Alzheimer's disease (AD), the most prevalent neurodegenerative disorder, involves the formation of the extracellular amyloid-ß (Aß) plaques and intracellular neurofibrillary tangles. The current therapies against AD are symptomatic with limited benefits but associated with major side effects. Inhibition of self-aggregation of Aß peptides into higher order cross-ß structure is one of the potential therapeutic approach which may counter oligomerization of Aß peptide. OBJECTIVE: The present study aimed to evaluate the neuroprotective and anti-inflammatory potential of a synthetic Pro-Drug type peptide (PDp) against Aß-induced toxicity in rat model of AD. METHODS: Intra-hippocampal microinjection of toxic Aß40 (IHAß40) by stereotaxic surgery was performed in the male Sprague-Dawley rats to generate an Aß-induced AD model. Sub-chronic toxicity of synthetic PDp using hematological, biochemical, and histopathological parameters was investigated. Evaluation of PDp on Aß-induced neurodegeneration and neuroinflammation was performed. RESULTS: PDp inhibits plaque formation with increase in Nissl granule staining in the rat hippocampus. Aß-induced toxicity associated imbalance in reactive oxygen species and antioxidant enzymes activity such as superoxide dismutase and catalase in the rat brain was overcome by PDp treatment. Tau protein hyperphosphorylation was normalized with PDp treatment. Also, the neuroinflammatory response was suppressed with PDp treatment. CONCLUSION: The present study depicts the potential neuroprotective role of PDp against Aß-induced toxicity in rat. PDp inhibits plaque formation thereby normalizing oxidative stress, inhibiting tau protein hyperphosphorylation, and suppressing neuroinflammatory responses. Future studies done in this direction will pave way for new therapeutic strategies.

Effects of chronic unpredictable mild stress induced prenatal stress on neurodevelopment of neonates: Role of GSK-3ß.

Prenatal stress (PNS) has gained attention with regard to its impact on hippocampal neurogenesis in neonates which serves as a risk factor for postnatal neurodevelopmental deficits. Evidences from animal models have suggested that depression responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal response via cortisol, is responsible for critical neurodevelopmental deficits in the offspring which is transduced due to gestational stress. But knowledge in the area of assessing the effects of maternal chronic unpredictable mild stress (CUMS) on neurogenesis and expression of some key signaling molecules in the offsprings are limited. We have used Wistar rats to induce PNS in offsprings by maternal CUMS during pregnancy. Prefrontal cortex (PFC) and hippocampus were assessed for biomarkers of oxidative stress, neurogenesis, neurodevelopmental signaling molecules and DNA damage in the male Wister offsprings. Our investigations resulted in sufficient evidences which prove how maternal psychological stress has widespread effect on the fetal outcomes via major physiological alteration in the antioxidant levels, neurogenesis, signaling molecules and DNA damage. PNS leads to the upregulation of GSK-3ß which in turn inhibited mRNA and protein expressions of sonic hedgehog (SHH), ß-catenin, Notch and brain derived neurotrophic factor (BDNF). The study explored multifaceted signaling molecules especially, GSK-3ß responsible for crosstalks between different neurodevelopmental molecules like SHH, Notch, BDNF and ß-catenin affecting neurodevelopment of the offsprings due to PNS.

Role of Hypothalamic-Pituitary-Adrenal Axis, Hypothalamic-Pituitary-Gonadal Axis and Insulin Signaling in the Pathophysiology of Alzheimer's Disease.

Alzheimer's disease (AD), the commonest progressive neurodegenerative disorder of the brain, is clinically characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. Recent studies suggest a relationship between the endocrinal dysregulation and the neuronal loss during the AD pathology. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and hypothalamic-pituitary-gonadal (HPG) axis regulating circulating levels of glucocorticoid hormones has been implicated in the pathophysiology of AD. Likewise, dysregulated insulin signaling, impaired glucose uptake and insulin resistance are some of the prime factors in the onset/progression of AD. In this review, we have discussed the changes in HPA and HPG axes, implicated insulin resistance/signaling and glucose regulation during the onset/progression of AD. Therefore, simultaneous detection of these endocrinal markers in the early or presymptomatic stages may help in the early diagnosis of AD. This evidence for implicated endocrinal functions supports the fact that modulation of endocrinal pathways can be used as therapeutic targets for AD. Future studies need to determine how the induction or inhibition of endocrinal targets could be used for predictable neuroprotection in AD therapies.

Influence of microglia and astrocyte activation in the neuroinflammatory pathogenesis of Alzheimer's disease: Rational insights for the therapeutic approaches.

Alzheimer's disease (AD), the most common progressive neurodegenerative disorder is characterized by the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles (NFTs). Increasing evidences suggest a link between neuroinflammation and neuronal dysfunction in AD, orchestrated by the progressive activation of microglial cells and astrocytes with the consequent overproduction of proinflammatory molecules. The concomitant release of anti-inflammatory mediators antagonizes the inflammatory processes and leading to the severity of the AD pathology. The simultaneous detection of these inflammatory molecules in the pre-symptomatic stage may help in the early diagnosis of the AD. We have discussed the impact of microglia and astrocytic cells, the principal agents in the neuroinflammation process, in relation to the progression of the AD. Modulation of the risk factors and targeting of these immune mechanisms could lead to better therapeutic or preventive strategies for the AD. Further studies need to determine, how the inhibition of inflammatory factors could be used for the AD alternative therapies.

Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment.

PURPOSE: Depression is one of the most prevalent, recurrent and life-threatening mental illnesses. However, the precise mechanism underlying the disorder is not yet clearly understood. It is therefore, essential to identify the novel biomarkers which may help in the development of effective treatment. METHODS: In this milieu, the profile of the brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) were considered as biomarkers in the light of pathophysiology of depression and its treatment. RESULTS: Previously, we have reported that BDNF level in the postmortem brain of suicide victims was significantly lower than those of normal controls. We also found decreased BDNF levels in the specific brain regions of the learned helplessness model of depression in rat, and was found to increase normal level following chronic fluoxetine hydrochloride treatment. NGF is another important member of neurotrophin, which is dysregulated in the pathophysiology of depression in some models of peripheral nerve damage and stress. The results shown evidences of the effect of antidepressants on modulating depression via the NGF in preclinical and clinical models of depression, but conflicted, therefore make it currently difficult to affirm the therapeutic role of antidepressants. CONCLUSIONS: Here, we review some of the preclinical and clinical studies aimed at disclosing the role of BDNF and NGF mediated pathophysiological mechanisms of depression and the new therapeutic approaches targeting those key molecules. In addition, an important link between BDNF, NGF and depression has been discussed in the light of current existing knowledge.

Bacopa monnieri alleviates paraquat induced toxicity in Drosophila by inhibiting jnk mediated apoptosis through improved mitochondrial function and redox stabilization.

Paraquat (PQ) is an organic chemical compound and a member of redox active family of heterocycles. In spite of its high toxicities, it is used as one of the potent herbicide throughout the world. Though its toxic manifestations are observed in different organs, its principal toxic effect is manifested in the brain leading to the development of Parkinsonian symptoms. PQ exposure adversely affects dopaminergic (DA-ergic) neuron-rich region in the substantia nigra pars compacta (SNPC) of brain in the animal models of Parkinson's disease (PD), thereby mimicking PD like symptoms. Currently, lack of a potential drug to counter the toxic effect of PQ makes the management difficult. Bacopa monnieri extract (BME) has been shown to have promising effect against neurodegenerative disorders. Therefore, the present study evaluated the role of BME against PQ induced toxicity in Drosophila model of PD, the results of which are reproducible in higher animal models including human subjects. Here, we showed that BME treatment attenuates acute PQ induced toxicity in Drosophila by decreasing mortality and improving climbing ability. BME functions by optimizing redox equilibrium, mitochondrial function and depreciating apoptosis level. The underlying mechanisms were attributed to optimization of active JNK and cleaved Caspase-3 activity along with transcriptional stabilization of the genes regulating oxidative stress and apoptosis (jnk, caspase-3, damb and nrf-2). These results showed therapeutic efficacy of BME against PQ toxicity in the brain. Our results pave the way for further detailed analysis of BME to combat the development of Parkinson's like symptoms following exposure to PQ toxicity in the brain of higher animal models.

Determination of potential oxidative damage, hepatotoxicity, and cytogenotoxicity in male Wistar rats: Role of indomethacin.

The present study demonstrated the indomethacin (INDO) induced oxidative stress, hepatotoxicity, and genotoxicity in male Wistar rats. Animals were orally administrated INDO at doses of 0.302 and 0.605 (mg/kg b.w.) for 2 weeks. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and lipid peroxidation (LPO) activities/levels were measured in the liver, kidney, and brain tissues. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, total bilirubin (TBIL) levels, and histopathological changes were determined in the liver tissues. Micronucleus frequency (micronucleus test) and DNA damage (comet assay) tests were performed in the bone marrow cells and leukocytes, respectively. Results show that INDO treatment decreased the GSH, SOD, and CAT levels/activities and increased the LPO, ALT, AST, ALP, and TBIL activities/levels. INDO induced significant hepatic injury and micronucleus and DNA damage. Thus, the current investigations confirm the oxidative stress, hepatotoxic, and genotoxic properties of INDO in the male Wistar rats.

Evaluation of phytomedicinal potential of perillyl alcohol in an in vitro Parkinson's Disease model.

Preclinical Research & Development Parkinson's disease (PD) is the second most common neurodegenerative disorder that affects approximately 10 million people worldwide. The risk of developing PD and similar neurodegenerative disorders increases with age and an estimated 4% people are diagnosed with the disease before reaching the age of 50. Oxidative stress, cytotoxicity, and mitochondrial dysfunction are common features exhibited in the development of PD. The 6-hyroxydopamine (6-OHDA) model of PD is one of the most well characterized and studied models of the disease. 6-OHDA, a neurotoxin, can induce most characteristic features of the disease, including mitochondrial dysfunction in-vivo and in-vitro. SH-SY5Y is a neuroblastoma cell line of human origin that has been used for dose response studies on PD in the past. Based on previous data, we have used SH-SY5Y cells as an in-vitro model of PD to analyse the phytomedicinal potential of perillyl alcohol (PA), a monoterpenoid obtained from essential oils of various plants such as sage, peppermint and lavender. We have found that pretreatment with PA (10 µM and 20 µM) mitigated 6-OHDA (150 µM) induced cytotoxicity in a dose-dependent manner. We observed marked restoration of cell viability and mitochondrial membrane potential (MMP) as well as reduced reactive oxygen species generation, Cytochrome c immunofluorescence and DNA fragmentation after treatment with PA. On the basis of on our data, we have come to the conclusion that PA demonstrates sufficient neuroprotective activity to provide new avenues in therapy of PD and its apparent target being restoration of MMP can lead to better understanding of the disease.

Evaluation of naproxen-induced oxidative stress, hepatotoxicity and in-vivo genotoxicity in male Wistar rats.

Naproxen (NP), a nonsteroidal anti-inflammatory drug (NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP; therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP. Male Wistar rats were administered NP orally at the doses of 38.91 and 65.78 mg/kg body weight for 14 days. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) activities/levels were measured in the liver, kidney and brain tissues. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and total bilirubin (TBIL) levels were measured in the liver tissues. Micronucleus frequency (micronucleus test MNT) and DNA damage (comet assay) were performed in the bone marrow cells and leukocytes, respectively. The results showed that NP treatment decreased the GSH levels and increased the SOD, CAT, LPO, ALT, AST, ALP and TBIL activities/levels compared to the control (p < 0.05). Results of MNT showed an increased micronucleus induction and comet assay showed a significant increase in DNA damage in the NP treated animals (p < 0.05). Treatment of NP resulted in the biochemical imbalance and induced oxidative stress that deteriorated the integrity of the cells, which caused significant damage to the genetic material and affected liver function in male Wistar rats. Therefore, NP is a potential genotoxic agent that induces genotoxicity and oxidative stress.

Evaluation of naproxen-induced oxidative stress, hepatotoxicity and in-vivo genotoxicity in male Wistar rats / 药物分析学报

Naproxen (NP), a nonsteroidal anti-inflammatory drug (NSAID), is used for the treatment of common pain, inflammation and tissue damage. Genotoxicity testing of NP is of prime importance as it represents the largest group of drugs to which humans are exposed. Not many genotoxic studies are reported on NP; therefore, the present study investigated the detailed genotoxic and oxidative stress properties of NP. Male Wistar rats were administered NP orally at the doses of 38.91 and 65.78 mg/kg body weight for 14 days. Reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and lipid peroxidation (LPO) activities/levels were measured in the liver, kidney and brain tissues. The aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) activities, and total bilirubin (TBIL) levels were measured in the liver tissues. Micronucleus frequency (micronucleus test MNT) and DNA damage (comet assay) were performed in the bone marrow cells and leukocytes, respectively. The results showed that NP treatment decreased the GSH levels and increased the SOD, CAT, LPO, ALT, AST, ALP and TBIL activities/levels compared to the control (p < 0.05). Results of MNT showed an increased micronucleus induction and comet assay showed a significant increase in DNA damage in the NP treated animals (p < 0.05). Treatment of NP resulted in the biochemical imbalance and induced oxidative stress that deteriorated the integrity of the cells, which caused significant damage to the genetic material and affected liver function in male Wistar rats. Therefore, NP is a potential genotoxic agent that induces genotoxicity and oxidative stress.

Important medicinal herbs in Parkinson's disease pharmacotherapy.

Parkinson's disease (PD) is the most common progressive neurodegenerative movement disorder affecting more than 10 million people worldwide. The characteristic hallmark of PD involves progressive loss of dopaminergic (DA-ergic) neuron in Substantia Nigra pars compacta (SNpc) region of the brain, however, aetiology of the disease still remains unclear. Mitochondrial dysfunction and oxidative insult are considered to be the key culprit. The current therapy available for PD primarily relies on Levodopa that offers the potential of slowing down disease progression to some extent but includes lot of side effects. Any potential drug capable of treating or halting the disease still remains to be identified. It is evident that redox stabilization and replenishment of mitochondrial function seem to be an important therapeutic approach against PD as both are required for optimal neuronal functioning. Enormous research done in this field has shown that some natural and synthetic products exhibit neuroprotective and anti-apoptotic potential by improving mitochondrial function and alleviating oxidative stress. Therefore, the present review aims to discuss some of the important medicinal natural herbs (Bacopa monnieri, Mucuna pruriens, Withania somnifera, Curcuma longa, Gingko Biloba, and Camellia sinensis) in context to their neuroprotective potential and also in the development of novel therapeutic strategies against PD.

Prenatal stress and depression associated neuronal development in neonates.

Prenatal maternal depression has its direct effects on early brain development deficits with permanent changes in neuroendocrine functions and impaired behavior in offsprings. Prenatal stress (PS) transmits its affect on developing fetus and on pregnancy outcomes in adult offsprings. This results in impaired neurodevelopment, delayed cognitive and motor development with impaired behavior towards stressful conditions. There are sufficient evidences in animal models suggesting depression responsive hypothalamic-pituitary-adrenal (HPA) axis and its hormonal response via cortisol, responsible for its critical effects in both the mother and offspring. We review the evidences how maternal psychological distress has widespread effect on fetal/birth outcomes via major physiological alteration in HPA axis, autonomic nervous system, neurotransmitters and signaling pathways. Knowledge void in the area of epigenetic processes like DNA methylation, histone acetylation and regulation of microRNA during prenatally stressed fetal neurodevelopment has to be filled up with properly defined controls. This aims the need to reexamine available literatures and to explore more directional approaches for prevention of PS as well as future treatment for the well being of the mother and fetus during critical physiological changes.

Anti-arthritogenic and cardioprotective action of hesperidin and daidzein in collagen-induced rheumatoid arthritis.

Atherosclerosis has been linked to chronic inflammatory processes. Changes in the levels of lipoproteins, especially low-density lipoprotein or its variants, as well as inflammatory markers are risk factors for the atherosclerosis. In the present study, an experimental model of rheumatoid arthritis was developed by administrating collagen suspension intradermally in the tail region of Wistar albino rats. At the same time, a suspension of hesperidin (50 mg/kg body weight) and daidzein (20 mg/kg body weight) was orally administrated. The compounds were given in the morning and evening for 21 days. Levels of inflammatory markers in the homogenate of knee joints of experimental rats as well as plasma lipoproteins were investigated. The administration of hesperidin and daidzein caused significant (p < 0.001) decrease in articular elastase activity, TNF-α, and malondialdehyde levels. Further, arthritis scoring and histological findings supported the anti-inflammatory actions of the test compounds. Interestingly, the test compounds also lowered the plasma low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglyceride but increased the level of high-density lipoprotein cholesterol. The test compounds thus ameliorated the risk factors of atherosclerosis. Furthermore, antioxidant roles of hesperidin as well as daidzein were evident from decrease in free radical load demonstrated as increase in total antioxidant level in plasma of arthritic animals treated with hesperidin and daidzein. In a separate in vitro experiment, enhanced free radical scavenging activity of hesperidin was demonstrated against 2,2-diphenyl-1-picrylhydrazyl and 2,2-azinobis-3-ethylbenzothiazoline-6-sulfonic acid. The anti-inflammatory, hypolipidemic, and antioxidant actions of the naturally occurring test compounds, particularly hesperidin, seem to be quite effective against rheumatoid arthritis and atherosclerosis. Thus, their consumption may be helpful in prevention or at least delaying the onset of these diseases in susceptible individuals.

In vivo induction of antioxidant response and oxidative stress associated with genotoxicity and histopathological alteration in two commercial fish species due to heavy metals exposure in northern India (Kali) river.

Heavy metals can significantly bioaccumulate in fish tissues. The step wise mechanism of heavy metal toxicities on fish health is still limited. The present study assessed the tissue-specific antioxidant response and oxidative stress biomarkers of commercially important fish species namely, Channa striatus and Heteropneustes fossilis inhabiting Kali River of northern India where heavy-metal load is beyond the World Health Organisation - maximum permissible limits. Heavy metals chromium (Cr), nickel (Ni), lead (Pb) and cadmium (Cd) were elevated in both fish species compared to recommended values of the Federal Environmental Protection Agency (FEPA), 1999 for edible fishes. Reduced glutathione (GSH), superoxide dismutase (SOD) and catalase (CATA) activities in all tissues (brachial, neural, renal and hepatic) were altered. Cellular lipid and protein compromisation in both fishes induced by heavy metals was determined by lipid peroxidation (LPO) and protein carbonylation (PC) assays. Micronucleus (MN) test of erythrocytes and comet assay of liver cells confirmed genotoxicity. Histopathology of the liver, kidney and brain of affected fishes was distorted significantly with its reference fishes thereby affecting the quality and quantity of these fish stocks. This raises a serious concern as these fishes are consumed by the local population which would ultimately affect human health.

Assessment of genotoxic induction and deterioration of fish quality in commercial species due to heavy-metal exposure in an urban reservoir.

The aim of the study was to evaluate the effect of heavy-metal contamination on two fish species (Channa striatus and Heteropneustes fossilis) inhabiting a small freshwater body of northern India. After being captured, each specimen was weighed, measured, and analyzed for heavy metals (chromium [Cr], nickel [Ni], and lead [Pb]). Accumulation of heavy metals was found to be significantly greater (p < 0.05) in different tissues (gill, liver, kidney, and muscle) of fishes captured from the reservoir than from the reference site. Levels of heavy-metal contamination in Shah jamal water was Cr (1.51 mg/l) > Ni (1.22 mg/l) > Pb (0.38 mg/l), which is significantly greater than World Health Organization standards. Bioaccumulation factor was calculated, and it was observed that Pb was most detrimental heavy metal. Condition factor was also influenced. Micronucleus test of fish erythrocytes and comet assay of liver cells confirmed genotoxicity induced by heavy-metal contamination in fishes. Heavy metals (Cr, Ni, and Pb) were increased in both fish species as determined using recommended values of Federal Environmental Protection Agency for edible fishes. This raises a serious concern because these fishes are consumed by the local populations and hence would ultimately affect human health.