Ali Karadeniz

THE EFFECTS OF PANAX GINSENG AND SPIRULINA PLATENSIS ON HEPATOTOXICITY INDUCED BY CADMIUM IN RATS

Cadmium is an environmental and industrial cumulative pollutant that affects many organs, specially the liver. The protective effect of Spirulina platensis and Panax ginseng on cadmium-induced oxidative stress and hepatotoxicity was evaluated in adult female Wistar albino rats. At the end of the 1-month experimental period, all animals were fasted for 12h and liver samples were taken for the determination of malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD) and nitric oxide (NO) levels. S. platensis and P. ginseng treatments showed marked decrease lipid peroxidation and increase of the endogenous antioxidants levels. The cadmium-induced histopathological changes were also minimized with the tested extracts. These results suggest that S. platensis and P. ginseng might play a role in reducing the toxic effect of cadmium and its antioxidant properties seem to mediate such a protective effect.

Royal Jelly Modulates Oxidative Stress and Apoptosis in Liver and Kidneys of Rats Treated with Cisplatin

Cisplatin (CDDP) is one of the most active cytotoxic agents in the treatment of cancer and has adverse side effects such as nephrotoxicity and hepatotoxicity. The present study was designed to determine the effects of royal jelly (RJ) against oxidative stress caused by CDDP injury of the kidneys and liver, by measuring tissue biochemical and antioxidant parameters and investigating apoptosis immunohistochemically. Twenty-four Sprague Dawley rats were divided into four groups, group C: control group received 0.9% saline; group CDDP: injected i.p. with cisplatin (CDDP, 7 mg kg−1 body weight i.p., single dose); group RJ: treated for 15 consecutive days by gavage with RJ (300 mg/kg/day); group RJ + CDDP: treated by gavage with RJ 15 days following a single injection of CDDP. Malondialdehyde (MDA) and glutathione (GSH) levels, glutathione S-transferase (GST), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities were determined in liver and kidney homogenates, and the liver and kidney were also histologically examined. RJ elicited a significant protective effect towards liver and kidney by decreasing the level of lipid peroxidation (MDA), elevating the level of GSH, and increasing the activities of GST, GSH-Px, and SOD. In the immunohistochemical examinations were observed significantly enhanced apoptotic cell numbers and degenerative changes by cisplatin, but these histological changes were lower in the liver and kidney tissues of RJ + CDDP group. Besides, treatment with RJ lead to an increase in antiapoptotic activity hepatocytes and tubular epithelium. In conclusion, RJ may be used in combination with cisplatin in chemotherapy to improve cisplatin-induced oxidative stress parameters and apoptotic activity.

SPIRULINA PLATENSIS PROTECTS AGAINST GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS

The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)‐induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague‐Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity. Copyright

Protective effect of Panax ginseng against serum biochemical changes and apoptosis in liver of rats treated with carbon tetrachloride (CCl4)

The purpose of this study was to investigate possible beneficial effects of Panax ginseng (PG) on carbon tetrachloride (CCl(4))-induced acute hepatotoxicity in rats. CCl(4) challenge elevated serum enzyme activities of liver and some biochemical parameters, but these effects were prevented by the pretreatment of rats with PG. Histologically, a great amount of mononuclear cells infiltration, necrotic cells and few fibroblasts were observed in liver of CCl(4) group. Also, CD68(+) and caspase-3 staining cells were diffused in both lobular and portal areas. However, PG pretreatment had a little influence on the number of caspase-3 immunopositive staining cells in the liver, but CD68(+) staining areas were significantly decreased in the PG+CCl(4) when compared to CCl(4) group. We conclude that PG treatment may play a protective role by enhancing liver enzyme activities and recovering biochemical parameters, and improving the changes in histological structure against CCl(4)-induced liver damages in rats.

Spirulina platensis feeding inhibited the anemia- and leucopenia-induced lead and cadmium in rats

In the present investigation, the effect of Spirulina platensis (Sp) was undertaken on rats fed with lead and cadmium including diet by using physiological, enzymehistochemical and stereological methods. For this aim, 50 rats were equally divided into five groups as control (C), lead (Pb), Spirulina+lead (Sp+Pb), cadmium (Cd), and Spirulina+cadmium (Sp+Cd). Red blood cell (RBC) and white blood cell (WBC) counts, packed cell volume (PCV), and haemoglobine (Hb) concentrations were determined by haemocytometric methods in blood samples collected on 30th day. Population of T lymphocyte was counted by the alpha-naphthyl acetate esterase (ANAE) staining method, and reticulocytes were counted by stereological method. The counts of RBC, WBC, and ANAE positive T lymphocyte, and the values of Hb, PCV, and MCHC were decreased in the Pb and Cd groups compared to control group. Also, the number of reticulocytes (polychromatofilic erythrocyte) increased in the Pb groups, whereas it decreased in the Cd group. On the other hand, these values were ceased by S. platensis in the treated groups. These results suggest that S. platensis supplementation may be useful in adjuvant treatment of leukemia and anemia caused by lead and cadmium toxication.

Pomegranate Seed Extract Attenuates Chemotherapy-Induced Acute Nephrotoxicity and Hepatotoxicity in Rats

Cisplatin (CDDP), one of the most active cytotoxic agents against cancer, has adverse side effects, such as nephrotoxicity and hepatotoxicity. The present study was designed to investigate the potential protective effect of pomegranate seed extract (PSE) against oxidative stress caused by CDDP injury of the kidneys and liver by measuring tissue biochemical and antioxidant variables and immunohistochemically testing caspase-3-positive cells. Twenty-four Sprague-Dawley rats were divided into 4 groups: control; CDDP: injected intraperitoneally with CDDP (7 mg/kg body weight, single dose); PSE: treated for 15 consecutive days by gavage with PSE (300 mg/kg per day); and PSE+CDDP: treated by gavage with PSE 15 days after a single injection of CDDP. The degree of protection against CDDP injury afforded by PSE was evaluated by determining the levels of malondialdehyde as a measure of lipid peroxidation. The levels of glutathione and activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase were estimated from liver and kidney homogenates; the liver and kidney were also histologically examined. PSE elicited a significant protective effect toward liver and kidney by decreasing the level of lipid peroxidation; elevating the levels of glutathione S-transferase; and increasing the activities of glutathione peroxidase, glutathione S-transferase, and superoxide dismutase. These biochemical observations were supported by immunohistochemical findings and suggested that PSE significantly attenuated nephrotoxicity and hepatotoxicity by the way of its antioxidant, radical-scavenging, and antiapoptotic effects. This PSE extract could be used as a dietary supplement in patients receiving chemotherapy medications.

Effects of melatonin on islet neogenesis and beta cell apoptosis in streptozotocin-induced diabetic rats: an immunohistochemical study

This investigation was carried out to explore the antidiabetic, antiapoptotic and neogenetic effects of melatonin (MLT) in streptozotocin-induced diabetic rats. Sixty-four male rats were assigned randomly to one of four groups for periods of 21 and 42 d as follows; i) control, ii) MLT, iii) diabetic (DM), and iv) DM + MLT. Immunohistochemical methods were used -with pancreatic tissue to determine the intensity of insulin, caspase-3 and Bcl-x(L) immune reactivities, and new islet formation. In untreated DM rats, BW loss, increased plasma glucose and MLT concentrations, as well as cytoplasmic degranulation and vacuolization were observed. We also observed a marked increase in the number of apoptotic caspase-3 positive cells and a few insulin- positive cells, but not antiapoptotic Bcl-x(L) positive cells. Observations in the DM + MLT-treated group revealed a high intensity of insulin- and antiapoptotic Bcl-x(L) immune reactivities at 21 and 42 d. Moreover, data indicated that MLT may cause beta cell proliferation and that new small islets originate from cells associated with ductal epithelium and from centroacinar cells by day 21. These data indicate that; i) MLT treatment may stimulate neogenesis in the pancreas of diabetic rats, and ii) MLTs antiapoptotic action may increase beta cell differentiation and caspase-3 inactivation or Bcl-x(L) activation.

Protective effect of L-carnitine against cisplatin-induced liver and kidney oxidant injury in rats

The present study was designed to investigate the protective effects of L-carnitine (LC) on changes in the levels of lipid peroxidation and endogenous antioxidants induced by cisplatin (cis-diamminedichloroplatinum II, CDDP) in the liver and kidney tissues of rats. Twenty-four Sprague Dawley rats were equally divided into four groups of six rats each: control, cisplatin, L-carnitine, and L-carnitine plus cisplatin. The degree of protection produced by L-carnitine was evaluated by determining the level of malondialdehyde (MDA). The activity of glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST), and superoxide dismutase (SOD) were estimated from liver and kidney homogenates, and the liver and kidney were histologically examined as well. L-carnitine elicited significant liver and kidney protective activity by decreasing the level of lipid peroxidation (MDA) and elevating the activity of GSH, GSHPx, GST, and SOD. Furthermore, these biochemical observations were supported by histological findings. In conclusion, the present study indicates a significant role for reactive oxygen species (ROS) and their relation to liver and kidney dysfunction, and points to the therapeutic potential of LC in CDDP-induced liver and kidney toxicity.