We investigated anti-hyperglycemic and anti-obese effects of Panax ginseng berry extract and its major constituent, ginsenoside Re, in obese diabetic C57BL/6J ob/ob mice and their lean littermates. Animals received daily intraperitoneal injections of Panax ginseng berry extract for 12 days. On Day 5, 150 mg/kg extract-treated ob/ob mice had significantly lower fasting blood glucose levels compared to vehicle-treated mice $(156{\pm}9.0\;mg/dl\;vs.\;243{\pm}15.8mg/dl,$ P<0.01). On Day 12, the extract-treated ob/ob mice became normoglycemic $(137{\pm}6.7\;mg/dl)$ and had significantly improved glucose tolerance. The overall glucose excursion during the two-hour intraperitoneal glucose tolerance test (IPGTT), calculated as area under the curve (AUC), decreased by $46\%$ (P<0.01) compared to vehicle-treated ob/ob mice. Glucose levels of lean mice were not significantly affected by the extract. The improvement in blood glucose levels in 150 mg/kg extracttreated ob/ob mice was associated with significant reduction in serum insulin levels of fed and fasting mice. Consistent with an improvement in insulin sensitivity, hyperinsulinemic euglycemic clamp study revealed a more than 2-fold increase in the rate of insulin-stimulated glucose disposal in treated ob/ob mice $(112{\pm}19.1\;vs.\;52{\pm}11.8{\mu}mol/kg/min$ for the vehicle group, P<0.01). In addition, 150 mg/kg extract-treated ob/ob mice, but not the lean mice, lost significant weight (from $51.7{\pm}1.9g\;on\;Day\;0\;to\;45.7{\pm}1.2$ on Day 12, P<0.01 compared to vehicle-treated ob/ob mice), associated with a significant reduction in food intake (P<0.05) and a very significant increase in energy expenditure (P<0.01) and body temperature (P<0.01). A 12-day treatment with 150 mg/kg Panax ginseng berry extract also significantly reduced plasma cholesterol levels in ob/ob mice. Additional studies demonstrated that ginsenoside Re, a major constituent of the ginseng berry, but not from the root, plays a significant role in anti-hyperglycemic action. This anti-diabetic effect of ginsenoside Re was not associated with body weight changes, suggesting that other constituents in the extract have distinct pharmacological mechanisms on energy metabolism. The identification of a significant anti-hyperglycemic activity in ginsenoside Re may provide an opportunity to develop a novel class of anti-diabetic agent.
The acidic saline animal model of pain has been suggested to mimic fibromyalgia (FM). Oligomeric proanthocyanidin complexes (OPC) from grape seeds are known to act as an antioxidant. We studied the effects of OPC on the pain threshold in the acidic saline animal model of pain. The left gastrocnemius muscle was injected with $100\;{\mu}l$ of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Control rats (n=5) received identical injections of physiological saline (pH 7.2) on the same schedule. Rats (n=10) with acidic saline injection were separated into two study subgroups. After measurement of pre-drug pain thresholds, rats were injected intraperitoneally with either saline or OPC 300 mg/kg. Paw withdrawal thresholds to pressure were again measured 60 min after intraperitoneal injection. Nociceptive thresholds were measured with a Dynamic Plantar Aesthesiometer by applying an increasing pressure to right or left hind paw until the rat withdrew the paw. Compared to baseline (day 0), acid injections produced mechanical hyper-responsiveness on day 7 (pre-drug) in these rats [p<0.05]. A potent antihyperalgesic effect was observed when rats were injected intraperitoneally with OPC 300 mg/kg [injected paw, p=0.001; contralateral paw, p=0.002]. OPC treatment decreased the expression of acid sensing ion channel 3 in the brain motor cortex area on immunohistochemical staining when OPC 300 mg/kg was administered intraperitoneally in the animal model of FM pain [p<0.05]. Further research is required to determine the efficacy of OPC treatments in FM pain in humans.
Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.
Objective : The inappropriate or excessive apoptosis has been known to be associated with neurodegenerative disorders including intracranial hemorrhage(ICH). Paeoniae radix, in traditional Korean medicine, has played its role as bloodnourisher and yin-astringent. In the present study, the effect of Paeoniae radix on the inhibition of neurodegeneration in the brain of rats after artificial ICH and on the resulting apoptosis was investigated. Methods : 30 rats were divided into 6 equal groups ; the sham-operation group, the hemorrhage-induction group, the hemorrhage-induction with 10, 50, 100, and 200 mg/kg Paeoniae radix-treated group, respectively. Stereotactic surgery was performed and collagenase was infused to induce ICH in the region of CA1 of hippocampus of rats. The sham group took only saline infusion. For 7 days after the surgery, 4 testing groups had intraperitoneal injections of Paeoniae radix extract. The step-down inhibitory avoidance task, measurement of neurodegeneration degree in the CA1 region of the hippocampus, and detection of caspase-3 and newly generated cells in the dentate gyrus were done after animal sacrifice. Results : Rats receiving Paeoniae radix extract showed increased latency time in the inhibitory avoidance task. The extension of neuron-deprived areas in the CA1 region was significantly suppressed in the Paeonia treated groups. Also expressions of caspase-3 in the CA1 region and cortex were significantly inhibited in the Paeonia treated groups. The cell proliferation was evaluated by means of BrdU methods and proved to be decreased in the Paeonia treated groups. Conclusion : These results suggest that Paeoniae radix has potential to suppress short-tenn memory loss after devastating neurologic accidents. Also it was proved that Paeoniae radix has a neuroprotective effect and alleviates central nervous complications following intracerebral hemorrhage. Furthermore, it may imply that this medicinal plant can be widely used for vascular dementia and other neurodegenerative disorders.
Cadmium (Cd) was administered by a series of weekly intraperitoneal injections at dose of 2mg/kg in rabbits and rats. The levels of malondialdehyde (MDA) and thromboxane $B^2(TXB_2)$ in platelet-rich plasma from Cd-poisoned animals were significantly higher than those of the control group. Furthermore, the inhibition of 6-keto-prostaglandin $F_{1{\alpha}}$, production in Cd-treated aorta ring was inversely related to the enhancement of platelet aggregation. These results suggest that Cd not only inhibits prostacyclin synthesis in the arterial endothelium, but also stimulates the platelet aggregation by enhancing thromboxane AZ production. These findings are assumed to support the evidence of an effect of Cd toxicity on the vascular wall and platelet function in raising arteriall pressure.
Jeong Chang Hwa;Moon Young Bong;Park In-Seok;Kim Dong Soo
Journal of Aquaculture
/
v.9
no.3
/
pp.287-291
/
1996
[ $F_2$ ] generation of gynogenetic diploids were produced in olive flounder, Paralichthys olivaceus, by brother-sister mating with full-sibling gynogenetic diploids ($F_1$). The induced ovulations and spawnings were conducted by using intraperitoneal injections of HCG (2,000 IU/kg body weight) with photoperiod controls. Floating rates of artificially ovulated eggs were ranged from 22.9 to $65.7\%$. Fertilization and hatching rates were ranged from 69.0 to $86.2\%$ and 36.8 to $85.8\%$, respectively. All of those three rates between two experimental groups were not significantly different (P>0.05). Average survival rates of $F_2$ generation of 40-day-old 효nogenetic diploid larvae were slightly lower than those of controls (P<0.05), however growth rates were much higher than those of their diploid controls.
The brown alga Saccharina japonica is consumed as a foodstuff in many countries. Carbon tetrachloride ($CCl_4$) is a potent hepatotoxin that is used to assess hepatotoxicity in animal models. This study assessed the protective effect of S. japonica extract (SJE) on $CCl_4$-induced acute liver injury in rats. Experimental rats were divided into the following three groups: control, $CCl_4$, and $CCl_4$+SJE; the latter two groups were given 150 or 300 mg SJE/kg orally for 10 days. Three hours after the final treatment, all rats-except for those in the control group-were administered intraperitoneal injections of $CCl_4$. One day later, blood and liver samples were collected for evaluation biomarker of levels. Aspartate transaminase (APT; GPT) and alanine aminotransferase (ALT; GOT) levels were markedly lower in the $CCl_4$+SJE group than the $CCl_4$ group. The hepatic superoxide dismutase (SOD) activity of the $CCl_4$+SJE group was significantly lower than that of the $CCl_4$ group. In comparison, glutathione S-transferase (GSH) and catalase (CAT) levels were significantly higher in the $CCl_4$+SJE group. Western blotting revealed that SJE attenuated the $CCl_4$-induced EGFR and MAPK activity in the liver. Thus, we conclude that SJE protects against $CCl_4$-induced hepatotoxicity.
Polychlorinated biphenyls (PCBs) are synthetic organic compounds with two benzene rings and well known environmental pollutants. This study examined the effect of persistent exposure to 2,$3^{\prime}$,4,$4^{\prime}$,5-pentachlorobiphenyl (PCB118) on the proinflammatory and proapoptotic factors in male rats. Male Sprague Dawley rats were administered weekly intraperitoneal injections of either PCB118 (20 mg/kg) dissolved in corn oil or corn oil alone. One week after 2 and 5 administrations, the rats were sacrificed by a pentobarbital injection. The effect of PCB118 on the expression of cyclooxygenase 2 (COX-2), cytosolic phospholipase A2 (cPLA2), peroxisome proliferator-activated receptor gamma, Bcl and Bcl-2-associated X protein (BAX) was investigated. The level of COX-2 and cPLA2 expression was higher in the PCB118-treated rats than the control. These results suggest that PCB118 has a proinflammatory effect in rats.
The objective of this study was to examine the effects of antioxidant vitamins on the cellular oxidant damage by observing the mitogenicity in the mouse spleen and the strand breaks of DNA in mouse blood induced by $AFB_2$. Intraperitoneal(i.p.) injections of vitamin C(VC) of 10 mg/kg and vitamin E(VE) of 63.8 mg/kg were repeatedly administered to male ICR mice of 6 weeks old at intervals of 4 times every 2 days. After one hour vitamin treatments, $AFB_1$ of 0.4 mg/kg was injected into the $AFB_2$ plus vitamin treated groups in the same way. On the other hands, into the $AFB_2$ only treated group, only $AFB_2$ was injected without vitamins in the same method as above. The results of the experiment are as follows ; as regard to comet assay, DNA strand breaks were clearly present and they formatted a typical comet tail in the mice blood of the $AFB_2$ only treated groups. However, comet tails apparently disappeared in $AFB_2$ plus antioxidant vitamins treated groups since oxidant damage was controlled in an almost similar level to the control group. Mitogenicity of the spleen also showed a similar tendency as before, and these differences were more remarkably observed in the reaction against Con-A, which is a T-cell mitogen. In these data, the statistical significance was p<0.01. The LDL and VLDL levels were 408.72, 504.47 mg/dl respectively in the $AFB_2$ only treated groups. Compared with the $AFB_1$ only treated groups, those of $AFB_2$ plus antioxidant vitamin treated groups decreased to 272.06(VC), 305.28 mg/dl(VE), respectively. On the other hand, HDL levels were diminished to 32.60, 29.60 mg/dl in $AFB_2$ only treated groups, compared to 42.23, 41.14 mg/dl in the $AFB_2$ plus antioxidant vitamins treated groups. But, blood glucose levels were not statistically significant.
Waly, Mostafa Ibrahim;Al Alawi, Ahmed Ali;Al Marhoobi, Insaaf Mohammad;Rahman, Mohammad Shafiur
Asian Pacific Journal of Cancer Prevention
/
v.17
no.12
/
pp.5071-5074
/
2016
Background: Azoxymethane (AOM) is a well-known colon cancer-inducing agent in experimental animals via mechanisms that include oxidative stress in rat colon and liver tissue. Few studies have investigated AOM-induced oxidative stress in rat liver tissue. Red seaweeds of the genera Hypnea Bryodies and Melanothamnus Somalensis are rich in polyphenolic compounds that may suppress cancer through antioxidant properties, yet limited research has been carried out to investigate their anti-carcinogenic and antioxidant influence against AOM-induced oxidative stress in rat liver. Objective: This study aims to determine protective effects of red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts against AOM-induced hepatotoxicity and oxidative stress. Materials and Methods: Sprague-Dawley rats received intraperitoneal injections of AOM, 15 mg/kg body weight, once a week for two consecutive weeks and then orally administered red seaweed (100 mg/kg body-weight) extracts for sixteen weeks. At the end of the experiment all animals were overnight fasted then sacrificed and blood and liver tissues were collected. Results: AOM treatment significantly decreased serum liver markers and induced hepatic oxidative stress as evidenced by increased liver tissue homogenate levels of nitric oxide and malondialdehyde, decreased total antioxidant capacity and glutathione, and inhibition of antioxidant enzymes (catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase and superoxide dismutase). Both red seaweed extracts abolished the AOM-associated oxidative stress and protected against liver injury as evidenced by increased serum levels of liver function markers. In addition, histological findings confirmed protective effects of the two red seaweed extracts against AOM-induced liver injury. Conclusion: Our findings indicate that red seaweed (Hypnea Bryodies and Melanothamnus Somalensis) extracts counteracted oxidative stress-induced hepatotoxicity in a rat model of colon cancer.
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