A.G. Telang

Protective effect of curcumin on cypermethrin-induced oxidative stress in Wistar rats.

The aim of present study was to investigate the protective effect of curcumin on cypermethrin-induced changes in blood biochemical markers and tissue antioxidant enzyme in rats. Rats were divided into six groups of six each: group I used as control and II and III groups were used as vehicle control. While, groups IV, V and VI were orally treated with curcumin (100 mg/kg body weight), cypermethrin (25 mg/kg body weight) and cypermethrin plus curcumin, respectively for 28 days. Serum biochemical markers were measured in the serum, and the levels of lipid peroxidation and antioxidant enzyme activity were determined in the liver, kidney and brain. Cypermethrin administration caused elevated level of blood biochemical markers in serum and lipid peroxidation in liver, kidney and brain. While the activities of non-enzymatic and enzymatic antioxidants levels were decreased except superoxide dismutase in liver, kidney and brain tissues. The presence of curcumin with cypermethrin significantly decreased the blood biochemical markers and lipid peroxidation but significantly increased the reduced glutathione, catalase and glutathione peroxidase level and preserved the normal histological architecture of the liver, kidney and brain. Our results indicate that curcumin can be potent protective agent against cypermethrin-induced biochemical alterations and oxidative damage in rats.

Oral nanoparticulate curcumin combating arsenic-induced oxidative damage in kidney and brain of rats:

Arsenic exposure through drinking water causes oxidative stress and tissue damage in the kidney and brain. Curcumin (CUR) is a good antioxidant with limited clinical application because of its hydrophobic nature and limited bioavailability, which can be overcome by the encapsulation of CUR with nanoparticles (NPs). The present study investigates the therapeutic efficacy of free CUR and NP-encapsulated CUR (CUR-NP) against sodium arsenite-induced renal and neuronal oxidative damage in rat. The CUR-NP prepared by emulsion technique and particle size ranged between 120 and 140 nm, with the mean particle size being 130.8 nm. Rats were divided into five groups (groups 1–5) with six animals in each group. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in Group 2; however, these animals were also administered with empty NPs, CUR (100 mg/kg body weight), and CUR-NP (100 mg/kg), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic exposure significantly increased serum urea nitrogen and creatinine levels. Arsenic increased lipid peroxidation (LPO), reduced glutathione content and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were depleted significantly in both kidney and brain. Treatment with free CUR and CUR-NP decreased the LPO and increased the enzymatic and nonenzymatic antioxidant system in kidney and brain. Histopathological examination showed that kidney and brain injury mediated by arsenic was ameliorated by treatment. However, the amelioration percentage indicates that CUR-NP had marked therapeutic effect on arsenic-induced oxidative damage in kidney and brain tissues.

Fipronil induced oxidative stress in kidney and brain of mice: Protective effect of vitamin E and vitamin C

Fipronil is a relatively new insecticide of the phenpyrazole group. Fipronil-induced effects on antioxidant system and oxidative stress biomarkers are yet to be studied in vivo. The present study was undertaken to evaluate fipronil-induced alterations in the blood biochemical markers and tissue antioxidant enzymes after oral exposure in mice and to explore possible protective effect of pre-treatment of antioxidant vitamins against these alterations. Mice were divided into eight groups containing control, test and amelioration groups. Mice in the test groups were exposed to different doses of fipronil, i.e., 2.5, 5 and 10 mg/kg bw, respectively for 28 days. Mice in the amelioration groups were treated with vitamin E or vitamin C (each at 100 mg/kg) 2 h prior to high dose (10 mg/kg) of fipronil. Fipronil exposure at three doses caused significant increase in the blood biochemical markers, lipid peroxidation and prominent histopathological alterations; while level of antioxidant enzymes was severely decreased both in kidney and brain tissues. Prior administration of vitamin E or vitamin C in the fipronil exposed mice led to decrease in lipid peroxidation and significant increase in activities of antioxidants, viz., glutathione, total thiol, superoxide dismutase and catalase. Vitamin E and vitamin C administration in fipronil exposed mice also improved histological architecture of the kidney and brain when compared with fipronil alone treated groups. Thus, results of the present study demonstrated that in vivo fipronil exposure induces oxidative stress and pre-treatment with vitamin E or C can protect mice against this oxidative insult.

Curcumin protects against cypermethrin-induced genotoxicity in rats

Cypermethrin is a synthetic pyrethroid insecticide used worldwide in agriculture, home pest control, protection of foodstuff and disease vector control. The aim of the present study was to investigate the protective effect of curcumin on cypermethrin-induced genotoxicity in rats. Administration of cypermethrin (25mg/kg, p.o.) for 28 days resulted in significant increase in the frequency of micronuclei formation in bone marrow cells and DNA damage in blood cells. Curcumin (100mg/kg, p.o.) administration caused significant reduction in micronuclei formation and, marked reduction in DNA damage. The present study revealed that presence of curcumin could diminish cypermethrin-induced genotoxicity in rats.

Evaluation of ameliorative effect of curcumin on imidacloprid-induced male reproductive toxicity in wistar rats.

This study was undertaken to investigate the toxic effects of imidacloprid (IM) on male reproductive system and ameliorative effect of curcumin (CMN) in male Wistar rats. For this purpose, IM (45 and 90 mg/kg, body weight) and CMN (100 mg/kg, body weight) were administered orally to the rats either alone or in combinations for a period of 28 days. At the end of experiment, male reproductive toxicity parameters (total sperm count and sperm abnormalities), testosterone level, steroidal enzymatic activity [3β‐hydroxysteroid dehydrogenase (3β‐HSD) and 17β‐HSD], and oxidative stress indicators were estimated in testis and plasma. IM treatments resulted in significant decrease (p < 0.05) in total epididymal sperm count, sperm motility, live sperm count, and increase (p < 0.05) in sperm abnormalities. Activities of gamma‐glutamyl transpeptidase, lactate dehydrogenase‐x, and sorbitol dehydrogenase were significantly increased (p < 0.05), while, 3β‐HSD and 17β‐HSD enzymatic activity along with testosterone concentration in testis and plasma were decreased significantly (p < 0.05) in IM‐treated rats. IM exposure resulted in significant increase (p < 0.05) in LPO and decrease (p < 0.05) in GSH level along with decreased activities of CAT, SOD, GPx, and GST. IM‐treated rats showed histopathological alterations in testis and epididymis. However, the reproductive toxicity parameters, oxidative stress indicators, and histopathological changes were minimized and functional restorations were noticed by co‐administration of CMN in IM‐treated rats. The results of this study suggest that IM‐induced male reproductive toxic effects could be ameliorated by CMN supplementation.

Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats.

We investigated the therapeutic effectiveness of the nanoparticle‐encapsulated curcumin (CUR‐NP) against sodium arsenite‐induced hepatic oxidative damage in rats. The CUR‐NP prepared by emulsion technique was spherical in shape with an encapsulation efficiency of 86.5%. The particle size ranged between 120 and 140 nm with the mean particle size being 130.8 nm. Rats were divided into five groups of six each. Group 1 served as control. Group 2 rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups 3, 4, and 5 were treated with arsenic as in group 2, however, they were administered, empty nanoparticles, curcumin (100 mg/kg bw) and CUR‐NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. Arsenic increased the activities of serum alanine aminotransferase and aspartate aminotransferase and caused histological alterations in liver indicating hepatotoxicity. Arsenic increased lipid peroxidation, depleted reduced glutathione and decreased the activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in liver. All these effects of arsenic were attenuated with both curcumin and CUR‐NP. However, the magnitude of amelioration was more pronounced with CUR‐NP. The results indicate that curcumin given in nano‐encapsulated form caused better amelioration than free curcumin.

Evaluation of imidacloprid-induced neurotoxicity in male rats: A protective effect of curcumin

The present study was carried out to evaluate the neurotoxic effect and biochemical alteration as a result of imidacloprid (IMI) exposure and potential protective role of curcumin (Cur) against it in rats. Rats were administered with IMI (45 and 90 mg/kg body weight; orally) and Cur (100 mg/kg body weight; orally) alone and in combinations for the period of 28 days. Significant decrease in spontaneous locomotor activity (SLA) and pain threshold were observed in animals treated with the IMI, while the effect was attenuated by the Cur co-treatment. Acetylcholinestaerase, ATPase and serum biochemicals such as creatine kinase, lactate dehydrogenase, sorbitol dehydrogenase and alkaline phosphatase levels were significantly decreased (p < 0.05) as result of IMI exposure and these enzyme levels were reversed in groups treated with the Cur in IMI treatments. Also, IMI caused a significant decrease (p < 0.05) in antioxidant enzymes activity and non-enzymes level with increase in lipid peroxidation (LPO), while Cur administration in IMI treatments restored the altered activity of antioxidant system with decrease in LPO. The IMI induced brain damage was minimized as result of Cur co-administration in rats. In conclusion, Cur restores the altered functions of biochemical markers and neurotoxicity in IMI exposed rats.

Immunomodulatory effects of nanocurcumin in arsenic-exposed rats

We evaluated whether the nanoformulation of curcumin could be more effective than free curcumin against arsenic-induced immune dysfunction in rats. Curcumin was encapsulated in polylactic-co-glycolic acid (PLGA). Nanocurcumin (CUR-NP) exhibited a spherical shape with the mean particle size of 130.8 nm. Rats were randomly divided into five groups of six each. Group I was kept as the control. In Group II, rats were exposed to sodium arsenite (25 ppm) daily through drinking water for 42 days. Groups III, IV and V were treated with arsenic as in Group II, however, they were administered with nanoparticle, curcumin (100 mg/kg bw) and CUR-NP (100 mg/kg bw), respectively, by oral gavage during the last 14 days of arsenic exposure. At term, serum and spleen were collected. Immune dysfunction was evaluated by assessing cellular and humoral immunities. Arsenic significantly decreased the splenic lymphocyte proliferation in response to the antigen -- Keyhole Limpet Hemocyanin (KLH) and mitogen -- concanavalin-A. Arsenic reduced both the delayed type hypersensitivity response and secondary antibody (IgG) response to KLH. It also reduced the lipopolysaccharide-stimulated nitric oxide production in splenic lymphocytes. Free curcumin and CUR-NP treatment significantly attenuated these arsenic-mediated effects. However, the magnitude of the effects indicates that CUR-NP has better ameliorative potential than free curcumin at the equivalent dose level.

Protective effect of curcumin against arsenic-induced apoptosis in murine splenocytes in vitro

Arsenic is a potent environmental pollutant and immunotoxic agent. Curcumin is a natural anti-oxidant used to treat a broad variety of diseases. Here, the effects were investigated of curcumin on sodium arsenite-induced apoptosis in murine splenocytes in vitro. Cells were exposed to sodium arsenite (NaAsO2, 5 µM) with and without curcumin (5 and 10 µg/ml) and incubated at 37°C for 12 h. NaAsO2 caused a decrease in cell viability and induction of apoptosis. These outcomes were concurrent with increases in the numbers of cells with reactive oxygen species generation, loss of mitochondrial transmembrane potential, an increase in the frequency of cells with sub-G1 DNA content, and DNA fragmentation. Co-administration of curcumin with the NaAsO2 caused significant recoveries in cell viability values and mitigation of the induced apoptosis-related molecular changes. A significant protection against apoptosis parameters in murine splenocytes simultaneously treated with NaAsO2 and curcumin suggested a protective efficacy of curcumin. From the results it is concluded that the immuno-modulation exerted by curcumin might be attributed to its multifaceted effects including its anti-oxidative and anti-apoptotic properties. These findings have implications not only for the under-standing of the toxicity of arsenic to murine splenocytes in vitro but are also potentially important for developing preventive and/or corrective strategies against/during chronic arsenicosis.

Firpronil induced spermotoxicity is associated with oxidative stress, DNA damage and apoptosis in male rats

The present study is the first to investigate and characterize the fipronil (FPN) induced spermotoxicity in male rats. Male rats were orally given FPN (2.5, 5.0 and 10 mg/kg/day) for 4 weeks. Epididymal sperms were collected and remaining testis was processed for histopathological evaluation. FPN treatment significantly reduced sperm density, motility, viability and per cent intact acrosome along with concomitant increase in spermatozoa abnormalities. Exposure of FPN caused excessive ROS generation, lipid peroxidation and alteration in mitochondrial membrane potential leading to apoptosis of spermatozoa in dose dependent manner. Higher FPN doses (5 and 10 mg/kg) markedly reduced the DNA integrity of spermatozoa. These data suggest that FPN causes male reproductive toxicity through oxidative stress induced DNA damage and apoptosis of spermatozoa.