M. Mobarak Hossain

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.

Sonic hedgehog, Wnt, and brain-derived neurotrophic factor cell signaling pathway crosstalk: potential therapy for depression

There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain‐derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF. Antidepressants are known to upregulate the adult hippocampal neurogenesis to treat depression. Shh plays an important role in adult hippocampal neurogenesis, and its downstream signaling components regulate the synthesis of Wnt proteins.

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.

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.

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

Preclinical Research & Development

Chromium oxide nanoparticle–induced biochemical and histopathological alterations in the kidneys and brain of Wistar rats

Chromium oxide nanoparticles (Cr2O3 NPs) have a wide range of applications in industry. They are used as pigments, catalysts, wear-resistant or high-temperature-resistant coating material and are used in liquid crystal displays. In view of ever escalating use of NPs, risk assessment becomes obligatory to ensure the safety of both human health and the ecosystem. The present study was designed and conducted to evaluate biochemical changes and histopathological alterations in kidneys and brain of rats, following exposure to Cr2O3 NPs. Male Wistar rats were divided into low-dose (50 µg/100 g body weight (bwt) groups and high-dose (200 µg/100 g bwt) groups. Each group type received oral administration of Cr2O3 NPs for multiple durations (single dosing, once daily for 7 days and once daily for 14 days, respectively). According to our data, this allotment presented a meaningful picture of NPs behaviour in different scenarios. In the kidneys and brain of Cr2O3 NPs-exposed animals, reactive oxygen species (ROS) production caused a significant increase in malondialdehyde (MDA) concentration along with a significant decrease in superoxide dismutase and glutathione levels, as compared to controls. Histopathological changes in these organs confirmed cellular injury and functional damage due to exposure to Cr2O3 NPs. In this study, we have distinguished pathological alterations consequent to deleterious oxidative stress due to enhanced ROS generation after Cr2O3 NPs exposure.