Fakiha Firdaus

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.

Perillyl Alcohol Alleviates Amyloid-β Peptides-Induced mitochondrial dysfunction and Cytotoxicity in SH-SY5Y Cells

Alzheimers disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia in elderly ( >65years of age). Excessive extra cellular deposits of amyloid beta (Aβ) are a pathological feature of AD. Aβ can cause cell death through oxidative damage; recent studies have implicated opening of mPTP as a detrimental event in AD-related mitochondrial dysfunctions. Over the past few years, natural compounds with antioxidant properties have shown promise for intervention in AD.

Ellagic acid mitigates arsenic‐trioxide‐induced mitochondrial dysfunction and cytotoxicity in SH‐SY5Y cells

In the current study, neuroprotective significance of ellagic acid (EA, a polyohenol) was explored by primarily studying its antioxidant and antiapoptotic potential against arsenic trioxide (As2O3)‐induced toxicity in SH‐SY5Y human neuroblastoma cell lines. The mitigatory effects of EA with particular reference to cell viability and cytotoxicity, the generation of reactive oxygen species, DNA damage, and mitochondrial dynamics were studied. Pretreatment of SH‐SY5Y cells with EA (10 and 20 μM) for 60 min followed by exposure to 2 μM As2O3 protected the SH‐SY5Y cells against the harmful effects of the second. Also, EA pre‐treated groups expressed improved viability, repaired DNA, reduced free radical generation, and maintained altered mitochondrial membrane potential than those exposed to As2O3 alone. EA supplementation also inhibited As2O3‐induced cytochrome c expression that is an important hallmark for determining mitochondrial dynamics. Thus, the current investigations are more convinced for EA as a promising candidate in modulating As2O3‐induced mitochondria‐mediated neuronal toxicity under in vitro system.

Ellagic acid attenuates arsenic induced neuro-inflammation and mitochondrial dysfunction associated apoptosis

Graphical abstract

Anxiolytic and anti-inflammatory role of thymoquinone in arsenic-induced hippocampal toxicity in Wistar rats

Arsenic (As) is a widely existing metalloid in the biosphere. Drinking water contamination by arsenic is a major route of human exposure, either by natural means or through industrial pollution. Numerous evidence form earlier reports suggest that arsenic exposure causes cerebral neurodegeneration which initiates behavioral disturbances concomitant to psychiatric disorders. Also, mood disorders in humans as well as in animals correlate with arsenic exposure; the present study is carried out to implore the neuroprotective potential of thymoquinone (TQ) in arsenic-stressed rats. TQ is an active component of Nigella sativa (Kalonji) seed oil. Arsenic exposure in the form of sodium arsenate (10 mg/kg/day; p.o) caused neurobehavioral deficits as evidenced by changes in locomotion and exploratory behavior in open-field and elevated plus maze tasks. Alongside this, arsenate also elevated hippocampal oxidative stress parameters like lipid peroxidation (TBARS) and protein carbonyl formation with a decrease in superoxide dismutase (SOD) and reduced glutathione (GSH) content. Genotoxicity assessment by Comet assay also showed prominent levels of DNA damage. Furthermore, arsenic also elevated hippocampal cytokine levels, TNF-α and INF-γ. However, TQ supplementation (2.5 and 5 mg/kg/day, p.o) preceded three days before arsenic administration, significantly attenuated arsenic-associated anxiogenic changes which majorly attributed to its antioxidant and anxiolytic potential. Also, TQ pre-treated rats expressed positive shifts in the hippocampal oxidative stress and cytokine levels with decreased DNA fragmentation. Thus, this study concludes that TQ might serve as a strong therapeutic agent for management of anxiety and depressive outcomes of arsenic intoxication.

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

Preclinical Research & Development

Thymoquinone alleviates arsenic induced hippocampal toxicity and mitochondrial dysfunction by modulating mPTP in Wistar rats

Arsenic is a pervasive environmental pollutant that is found in ground waters globally and is related to numerous morbidities in the high-risk population areas in countries including Bangladesh, India, and the USA. Arsenic exposure has been ubiquitously reported for exacerbating free radical generation, mitochondrial dysfunction, and apoptosis by interfering with the mPTP functioning. Over the past decades, nutraceuticals with antioxidant properties have shown promising efficacy in arsenic poisoning. In the present study, we have examined, the protective efficacy of thymoquinone (TQ), an active component of seed oil of Nigella sativa with antioxidant and anti-inflammatory activity on arsenic-induced toxicity in hippocampi of Wistar rats. In our results, arsenic conditioning (10 mg/kg b.wt.; p.o.) for 8 days has caused a significant increase in intracellular ROS generation, mitochondrial dysfunction and apoptotic events. On the contrary pretreatment with TQ (2.5 and 5 mg/kg b.wt.; p.o.) inhibited arsenic-induced mitochondrial dysfunction such as lowering of mitochondrial membrane potential (Δψm). Our results indicated that the neuroprotective efficacy of TQ in arsenic-induced stress is mediated through or in part by inhibition of mPTP opening. Demonstration of neuroprotective action of TQ provides insight into the pathogenesis of arsenic-related neuropathological morbidities.