Volume 30, Issue 2

Toxic metals, including excessive levels of essential metals tend to change biological structures and systems into either reversible or irreversible conformations, leading to the derangement of organ functions or ultimate death. Nickel, a known heavy metal is found at very low levels in the environment. Nickel is available in all soil types and meteorites and also erupts from volcanic emissions. In the environment, nickel is principally bound with oxygen or sulfur and forms oxides or sulfides in earth crust. The vast industrial use of nickel during its production, recycling and disposal has led to widespread environmental pollution. Nickel is discharged into the atmosphere either by nickel mining or by various industrial processes, such as power plants or incinerators, rubber and plastic industries, nickel-cadmium battery industries and electroplating industries. The extensive use of nickel in various industries or its occupational exposure is definitely a matter of serious impact on human health. Heavy metals like nickel can produce free radicals from diatomic molecule through the double step process and generate superoxide anion. Further, these superoxide anions come together with protons and facilitate dismutation to form hydrogen peroxide, which is the most important reason behind the nickel-induced pathophysiological changes in living systems. In this review, we address the acute, subchronic and chronic nickel toxicities in both human and experimental animals. We have also discussed nickel-induced genotoxicity, carcinogenicity, immunotoxicity and toxicity in various other metabolically active tissues. This review specifically highlighted nickel-induced oxidative stress and possible cell signaling mechanisms as well.

Wernicke encephalopathy (WE) and Korsakoff psychosis (KP), together termed Wernicke–Korsakoff syndrome (WKS), are distinct yet overlapping neuropsychiatric disorders associated with thiamine deficiency. Thiamine pyrophosphate, the biologically active form of thiamine, is essential for multiple biochemical pathways involved in carbohydrate utilization. Both genetic susceptibilities and acquired deficiencies as a result of alcoholic and non-alcoholic factors are associated with thiamine deficiency or its impaired utilization. WKS is underdiagnosed because of the inconsistent clinical presentation and overlapping of symptoms with other neurological conditions. The identification and individualized treatment of WE based on the etiology is vital to prevent the development of the amnestic state associated with KP in genetically predisposed individuals. Through this review, we bring together the existing data from animal and human models to expound the etiopathogenesis, diagnosis, and therapeutic interventions for WE and KP.

Introduction There is a dearth of studies assessing the efficacy and immunological improvement in patients started on antiretroviral therapy (ART) in India. This study was undertaken to assess the 2-year treatment outcomes in HIV-positive patients initiated on ART in a tertiary-care hospital. Methods After approval from the Institutional Ethics Committee, adult HIV-positive patients from a tertiary-care hospital, initiated on ART between January 2013 and February 2015, were included in the study. Data on clinical and immunological parameters were obtained from medical case records over a period of 2 years after initiation of therapy. Intention-to-treat analysis was done using a descriptive approach, using SPSS version 15 (SPSS Inc. Released 2006. SPSS for Windows, Version 15.0. Chicago, SPSS Inc.). A logistic regression analysis was done to assess the predictors for poor outcomes. A p-value <0.05 was considered statistically significant. Results ART was initiated in 299 adult patients. At 1 and 2 years, the median (interquartile range) change in CD4 + cell count was 65 (39, 98) cells/mm 3 and 160 (95, 245) cells/mm 3 . The change observed after 2 years of treatment initiation was statistically significant compared with that after 1 year. Three deaths occurred during the study period and 28 were lost to follow-up. Male sex, presence of at least one opportunistic infection at the start of therapy, and baseline CD4 + count <50 cells/mm 3 were associated with poor immunological recovery. Conclusions With long-term treatment and regular follow-up, sustained clinical and immunological outcomes can be obtained in resource-limited settings.

Background Tetracera alnifolia Willd. (Dilleniaceae) is used in traditional African Medicine for the treatment of headache, abdominal pain, and rheumatism. Hence, this study sought to investigate the antinociceptive and anti-inflammatory effects of the hydroethanolic leaf extract of T. alnifolia (HeTA) in rodents. Methods Antinociceptive activity was evaluated using the acetic acid-induced writhing, formalin-/capsaicin-induced paw licking and hot plate tests in mice. The contribution of opioidergic, l -arginine-nitric oxide, and ATP-sensitive potassium channel pathways in HeTA-induced antinociception was also evaluated. The anti-inflammatory effect was assessed using the carrageenan-induced paw edema, xylene ear edema, cotton pellet granuloma, and complete Freund’s adjuvant (CFA)-induced arthritis in rats. Results HeTA (100, 200, and 400 mg/kg, p.o.) produced significant (p<0.05) decrease in mean number of acetic acid-induced writhing, time spent licking paw in formalin, and capsaicin tests as well as time course increase in nociceptive reaction latency in hot plate test. HeTA-induced antinociception was prevented by pretreatment of mice with naloxone (non-selective opioid receptor antagonist), l -arginine (nitric oxide precursor), or glibenclamide (ATP-sensitive potassium channel blocker). HeTA (100 mg/kg, p.o.) produced a significant anti-inflammatory effect against carrageenan-induced rat paw edema (1–5 h), xylene-induced ear edema, cotton pellet-induced granuloma formation, and CFA-induced arthritis in rats. The effects of HeTA in various models were similar to the effect of the standard reference drugs. Conclusions Findings from this study showed that HeTA possesses antinociceptive effect possibly mediated through peripheral opioid receptors with activation of l -arginine-nitric oxide and ATP-sensitive potassium channel pathway as well as anti-inflammatory activity.

Background Eugenol is the foremost constituent of clove oil and widely distributed in many plants. It possesses many pharmaceutical applications, including antioxidant, anti-inflammatory, and anti-tumorigenic properties, among others. This study evaluates the influence of eugenol on oxidative stress biomarkers in the liver of carrageenan-induced arthritis (CIA) rats. Methods Sixty albino rats were randomly divided into 10 (n=6) groups. Group I is the control group that received saline solution orally. Groups II and VII rats received 2.5 mg/kg of eugenol orally (EUG-2.5). Rats in groups III/VIII and IV/IX received 5 and 10 mg/kg of eugenol orally (EUG-5 and EUG-10), respectively. Groups V and X received 0.2 mg/kg of dexamethasone (DEX-0.2) orally. Groups VI to X were injected with 1% carrageenan intra-articularly. Behavioral studies were conducted after 21 days of treatment. Thereafter, the animals were sacrificed, and the livers were isolated and used for biochemical analysis. Results Reduced body weight in arthritic rats was recorded compared to normal controls. Reduced tibiofemoral joint edema and increased spontaneous movement were observed in CIA rats with decreased superoxide dismutase, catalase, reduced glutathione (GSH), glutathione peroxidase, and GSH S-transferase activities compared with the normal control group. Increased endogenous enzyme activities and decreased elevated lipid peroxidation were also observed after eugenol treatment. Conclusion Eugenol ameliorates carrageenan-induced oxidative stress in the liver of arthritic rats.

Background Selective serotonin reuptake inhibitors (SSRIs) have recently become potential candidates for a new therapeutic approach to ulcer and gastric bleeding. Heat shock protein 70 (Hsp70) plays an important role in cellular resistance to nonsteroidal anti-inflammatory drugs (NSAIDs). However, there is lack of evidence that fluvoxamine recruits Hsp70 to affect stress-induced gastric ulcer. Therefore, we investigated the effect of fluvoxamine on NSAID- and stress-induced gastric ulcer and the possible involvement of Hsp70. Methods ICR mice were used in the study. Stress induction was made by the water-immersion-plus-restraint method. NSAID-induced gastric ulcer was produced by oral administration of indomethacin. Fluvoxamine was given orally 30 min before stress induction and indomethacin treatment. Results Stress and indomethacin treatment significantly increased the ulcer index and intraluminal bleeding score. Stress and indomethacin treatment also significantly increased the expression of Hsp70. Fluvoxamine significantly decreased the ulcer index and intraluminal bleeding in both ulcer models. Moreover, fluvoxamine further increased the expression of Hsp70 in the gastric tissue of stress- and indomethacin-treated mice. Conclusions Our results indicate that fluvoxamine may have a protective effect against stress- as well as NSAID-induced gastric ulcer. In addition, the present study suggests the possible involvement of Hsp70 in the amelioration of gastric ulcer by fluvoxamine.

Background Cisplatin (CP) is a novel drug of choice in the treatment of cancer but its major limitation is nephrotoxicity, which is dose limiting. Andrographis paniculata (AP) is a common Indian dietary component. It is well known for its medicinal properties. This present study investigated the nephroprotective effect of ethanol leaf extract of Andrographis paniculata (EEAP) on CP-induced nephrotoxicity. Methods CP was used to induce nephrotoxicity in male Wistar rats to study the effect of EEAP on renal damages using hematological parameters, biochemical parameters, histology, and immunohistochemistry studies. Results The effects of EEAP were determined by CP-induced changes in different kidney tissue on antioxidant enzymes, markers of oxidative stress, serum creatinine, and urine parameters. Administration of EEAP (200 mL/kg and 400 mg/kg orally), prior to and following a single dose CP treatment (10 mg/kg i.p), significantly mitigated the CP-induced decrease in antioxidant enzymes, and increase in markers of oxidative stress, serum creatinine, and urinary protein. On histopathological examination of the kidney tissue, there was severe glomerular degeneration and infiltration of inflammatory cells in CP only treated rats, mild glomerular degeneration, and infiltration of inflammatory cells in EEAP pre-treated rats. Furthermore, EEAP activated Nrf2 and mitigated Kim-1 pathways in CP-induced nephrotoxicity. Conclusions The results showed the protective effect of EEAP against CP-induced nephrotoxicity.

Background Aspartame (ASP) is used for treatment of obesity and diabetes mellitus. This study was designed to illustrate the biochemical responses and histopathological alterations besides the genotoxicity of ASP alone or with l -carnitine (LC) in the liver of rats. Methods Animals were separated into six groups: control, lower dose of ASP (ASP-LD; 75 mg/kg), higher dose of ASP (ASP-HD; 150 mg/kg), l -carnitine (LC; 10 mg/kg), ASP-LD plus LC, and ASP-HD plus LC. Treatment was carried out orally for 30 consecutive days. Results ASP raised the activity of some enzymes of liver markers and disturbed the lipid profile levels. The hepatic reduced glutathione (GSH) levels, the marker enzymes of antioxidant activities, were obviously diminished, and, possibly, the lipid peroxidation, C-reactive protein, and interleukins levels were increased. ASP significantly increased the DNA deterioration in comparison with the control in a dose-dependent manner. LC prevented ASP-induced liver damage as demonstrated by the enhancement of all the above parameters. Results of histopathological and electron microscopic examination proved the biochemical feedback and the improved LC effect on liver toxicity. Conclusions The co-treatment of LC showed different improvement mechanisms against ASP-induced liver impairment. So, the intake of ASP should be regulated and taken with LC when it is consumed in different foods or drinks to decrease its oxidative stress, histopathology, and genotoxicity of liver.

Background Altered lifestyle and urbanization have potentially increased the prevalence of polycystic ovary syndrome (PCOS) among the women in India. The aim of the present study was to evaluate the autonomic function and subclinical cognition impairment using evoked potentials in PCOS-affected young adolescents. Methods This was a cross-sectional study, approved by Indian Medical of Council Research as a short-term student project. The study was performed with adolescent girls (age group, 10–18 years) diagnosed as having PCOS, attending the Department of Obstetrics and Gynecology at Sri Manakula Vinayagar Medical College and Hospital, Puducherry. Autonomic function was evaluated using heart rate variability and cognition employing auditory evoked potentials (P300 latency and amplitude) among the control group (n=30) and the PCOS group (n=30). Results Our study reports indicated that autonomic functions were significantly affected among the PCOS group compared to the control group (p=0.03), with sympathetic dominance and decreased vagal tone. P300 latency was prolonged and amplitude was decreased among the PCOS group, but the results were not statistically significant when compared to the control group. Body mass index showed significant correlation with sympathovagal imbalance. Conclusion The study indicates that autonomic functions are significantly altered in the PCOS group. Subclinical cognition impairment is seen among the PCOS group but is not pronounced enough to be proven statistically. This study informs adolescent girls to make early lifestyle changes as soon as possible before any significant clinical impairment occurs.

Background Salacial lehmbachii stem bark is used traditionally for the treatment of diabetes mellitus and its associated complications. Treatment of diabetes is necessary to reduce these complications. Methods In this study, the antidiabetic and antihyperlipidemic potential of S. lehmbachii ethanol stem bark extract was evaluated in alloxan-induced diabetic rats at a dose of 100 mg/kg, 200 mg/kg, and 400 mg/kg p.o. daily for 21 days. Blood glucose levels, serum total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), and very low density lipoprotein (VLDL) were assessed in the animals. Results Treatment of alloxan-induced diabetic rats with S. lehmbachii stem bark extract showed significant (p<0.01) reduction in blood glucose levels when compared with diabetic control. The elevated levels of serum cholesterol, triglycerides, LDL, and VLDL were significantly (p<0.01) reduced by S. lehmbachii stem bark extract, while the level of HDL significantly (p<0.01) increased. Conclusions The results obtained suggest that S. lehmbachii stem bark extract has the potential to treat diabetes condition and hyperlipidemic disorders.

Background Liver dysfunction is a predominant complication of diabetes. Herbal remedies such as garlic are commonly used for reducing diabetic complications. In this study the effect of garlic extract on glucose level, liver enzymes activities in the serum and nitric oxide (NO) level, oxidative stress status, and histology in the liver tissues of streptozotocin-induced diabetes (type 1) was investigated. Methods Twenty-four adult male Wistar rats were randomized and divided into four groups: control rats, diabetic rats, diabetic rats treated with garlic, and garlic-treated normal rats. Glucose level and liver enzymes activities were determined by colorimetric assay in the serum. NO levels by Griess method, oxidative stress parameters including malondialdehyde (MDA), total oxidative status (TOS), and total antioxidant capacity (TAC) by spectrophotometric method, and histopathological examination by hematoxylin and eosin staining method were evaluated in the liver tissues. Results Glucose level, liver enzymes activities, MDA, TOS, and NO levels were increased and TAC level decreased significantly in diabetic rats in comparison with control rats (p<0.01); whereas, after oral administration of garlic, glucose level, liver enzymes activities, MDA, TOS, and NO levels were decreased and TAC level increased significantly near to the normal levels (p<0.05). Conclusion The results showed the hypoglycemic and antioxidant effects of garlic in the livers of type 1 diabetic rats.

Background Based on our previous ethnobotanical survey, the non-investigated Saharan plant Anabasis aretioides Coss. & Moq., growing in the region of Errachidia, was selected for pharmacological investigation. In Moroccan traditional medicine, A. aretioides is being used for diabetes treatment. Thus, the current work aims at evaluating the antidiabetic, antioxidant, and antibacterial activities of the plant in relation to the digestive tract. Methods The different parts of the plant (aerial parts, roots, seeds) were extracted with methanol (MeOH) and screened in enzymatic assays for their inhibitory potential against α-amylase and α-glucosidase, as well as antioxidant and antibacterial activities. Furthermore, the phenolic compounds were analyzed using HPLC-DAD-QTOF-MS. Results The MeOH extracts of A. aretioides aerial parts, roots, and seeds, respectively, inhibited α-amylase (IC 50 of 3148.07 μg/mL, 2440.20 μg/mL, 3395.71 μg/mL) and α-glucosidase (IC 50 of 2940.59 μg/mL, 3521.81 μg/mL, 3393.83 μg/mL). Moreover, compared to aerial parts and seeds, the plant roots exhibited higher antioxidant capacity and a potent reducing power. In resazurin microplate assay, the plant parts displayed a minimal inhibitory concentration (MIC) ranging from 7.81 mg/mL to 31.25 mg/mL. Chemical analysis revealed 25 phenolic compounds, with chlorogenic acid as the main phenolic compound in the aerial parts, hesperidin in roots, and quercitrin in seeds. Conclusion Anabasis aretioides cited for treatment of diabetes shows promising antioxidant and antibacterial properties, as well as an ability to inhibit digestive enzyme, including α-amylase and α-glucosidase. Thus, our results explain in part the traditional use of this Saharan medicine and open doors for further in vivo mechanistic and functional studies.

Background A significant relationship has been documented in the literature between the autonomic nervous system imbalance and cardiovascular mortality. In patients with autonomic failure, water ingestion has been shown to increase blood pressure (BP), induce bradycardia, and cause low heart rate variability (HRV). A few studies showed the altered HRV as an acute effect of ice water intake in healthy subjects. None of the studies have shown light on the relationship of BP and HRV to ice water intake in obese and overweight subjects. The present study is aimed to correlate BP and HRV with body mass index (BMI) after ice water ingestion. Methods This cross-sectional study included a total of 60 subjects of both sexes aged between 18 and 24 years old. Subjects were assigned into three groups based on their BMI: normal, overweight, and obese. Before and after ice water ingestion, BP and HRV parameters were recorded and compared between the groups. Statistically data were analyzed by Student’s paired t-test and one-way analysis of variance. Results Basal HF was significant (p<0.05) in all three groups after ice water ingestion [ F (2, 27), 44.1; p-value, 0.02]. After ice water ingestion, all HRV values were significant (p<0.001) in the three groups. The post-hoc Tukey HSD test demonstrated the less mean score for mean RR interval, standard deviation of all NN interval, standard deviation of differences between adjacent, HF and high for HR, LF, and LHR in overweight and obese subjects. Conclusions Because of the effective buffering system, healthy subjects showed increased HR and unchanged BP. Overweight and obese subjects showed decreased HR and increased BP.

Background Sulfotransferases (SULTs) are phase II drug-metabolizing enzymes. SULTs also regulate the biological activities of biological signaling molecules, such as various hormones, bile acids, and monoamine neurotransmitters; therefore, they play critical roles in the endocrine and nervous systems. People are subject to various kinds of physical, chemical, toxicological, physiological, and psychological stresses at one time or another. The study of the effects produced by stress may lead to finding novel remedies for many disease conditions. The effect of repeated restraint stress on rat SULT expression has not been studied. Methods This study involves the effect of repeated restraint stress on SULT1A1 expressions. Male Sprague-Dawley rats (n=4) were subjected to repeated restraint stress 2 h/day for 7 days. Protein and RNA expression of SULT1A1 were analyzed by western blot and quantitative real time reverse transcription polymerase chain reaction, respectively, in important tissues. Results We observed that repeated restraint stress increased the expression of SULT1A1 in the liver, adrenal glands, cerebellum, hypothalamus, and cerebral cortex in male rats. Patterns of enhanced expression were observed at both mRNA and protein level, indicating that repeated restraint stress stimulates enzyme expression at the transcriptional level. Conclusions Changes of SULT1A1 expression in important tissues caused by repeated restraint stress will have a significant effect on drug metabolism and xenobiotics detoxification. The significant changes in endocrine glands and brain sections may also cause disturbances in hormone homeostasis, therefore leading to disease conditions. This report provides clues for the understanding of the effect of stresses on health.

Adverse drug reaction (ADR) is a form of unwanted reaction and is the crucial reason for illness and death. Tramadol-induced parkinsonism is a kind of ADR that occurs after the repeated intake of tramadol. Long-term exposure to tramadol has been known to induce tremor and alter the functioning of dopamine. This case report introduces a 75-year-old woman diagnosed with tramadol-induced parkinsonism due to the administration of tramadol for the treatment of post-operated (breast cancer) acute onset of severe pain on the left side of the chest. The assessment of the offending drug was carried out via Naranjo probability scale. A score of 6 was reported for this patient, defining tramadol as a probable cause of this reaction. For the management of the drug-induced parkinsonism, levodopa/carbidopa was prescribed and the symptoms related to parkinsonism resolved within a week. The age of the patient and the female gender is considered to be the main risk factor for the occurrence of such reaction. This case report is an attempt to spread awareness about the negative consequences of long-term use of tramadol in old patients. Thus, the medical practitioners must be very careful while administering tramadol to the old aged population.