ABSTRACT
BACKGROUND: Steroid-induced avascular necrosis of the femoral head has a complex biological process, and its pathogenesis is unknown. To date, there is no effective treatment in clinical practice. Therefore, exploring the etiology of steroid-induced avascular necrosis of the femoral head is still an important content of research in this field. OBJECTIVE: To explore the effect of grape seed proanthocyanidins on osteocyte apoptosis due to steroid-induced osteonecrosis of the femoral head. METHODS: Twenty-seven Japanese white rabbits were randomly divided into three groups. The model group was intravenously injected with E. coli endotoxin, 100 μg/kg, twice at an interval of 24 hours. Two injections of E. coli endotoxin were followed by intramuscular injection of methylprednisolone 20 mg/kg, for 3 times. The interval was 24 hours. The treatment group was intravenously injected with E. coli endotoxin, 100 μg/kg, twice at an interval of 24 hours. After the second injection of E. coli endotoxin, methylprednisolone 20 mg/kg and grape seed proanthocyanidin extract 200 μg/kg were injected intramuscularly three times at an interval of 24 hours. The control group was treated with the same dose of saline intravenously. The animals were killed by air embolization at the 4th week after the last injection. Under the relatively aseptic condition, the bilateral femoral heads were routinely fixed, decalcified, embedded and sliced. Histomorphological observation and hematoxylin-eosin staining were performed to count empty bone lacunae under light microscope. Hoechst staining was used to detect cell apoptosis. The expressions of Caspase-9 and Bcl-2 in the femoral head were detected by immunohistochemical staining.
ABSTRACT
BACKGROUND/AIMS: To investigate the gastroprotective effects of grape seed proanthocyanidin extracts (GSPEs) against nonsteroid anti-inflammatory drug (NSAID)-induced gastric mucosal injury in rats. METHODS: Sprague-Dawley rats were randomly allocated to the normal control, indomethacin, low-dose GSPE, high-dose GSPE and misoprostol groups. All groups except the normal control group received pretreatment drugs for 6 consecutive days. On the 5th and 6th day, indomethacin was administered orally to all groups except for normal control group. The microscopic features of injury were analyzed. The levels of gastric mucosal glutathione, gastric mucosal prostaglandin E2 (PGE2), and proinflammatory cytokines were investigated. RESULTS: The total areas of ulceration in the GSPE and misoprostol groups were significantly decreased compared with the indomethacin group (p<0.05). However, a difference in ulcer formation among the drug treatment groups was not observed. Meanwhile, the glutathione levels in the high-dose GSPE group were higher than those of both the indomethacin and misoprostol groups (p<0.05) and were similar to those of the normal control group. Additionally, there was no difference among the groups in the levels of gastric mucosal PGE2 and proinflammatory cytokines. CONCLUSIONS: High-dose GSPE has a strong protective effect against NSAID-induced gastric mucosal injury, which may be associated with the antioxidant effects of GSPE.
Subject(s)
Animals , Rats , Antioxidants , Cytokines , Dinoprostone , Glutathione , Grape Seed Extract , Indomethacin , Misoprostol , Proanthocyanidins , Rats, Sprague-Dawley , Seeds , Ulcer , VitisABSTRACT
Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P < 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1beta and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.
Subject(s)
Animals , Humans , Male , Rats , Analgesics/administration & dosage , Antioxidants/administration & dosage , Bone Resorption , Disease Models, Animal , Gene Expression Regulation , Interleukin-1beta/genetics , Iodoacetates/administration & dosage , Knee Joint/drug effects , Matrix Metalloproteinase 13/genetics , Osteoarthritis/chemically induced , Pain , Plant Extracts/administration & dosage , Proanthocyanidins/administration & dosage , Rats, Wistar , Seeds , Tomography, Emission-Computed , Tyrosine/analogs & derivatives , Vitis/immunologyABSTRACT
Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weight bearing ability. Joint damage was assessed using histological and microscopic analysis and microcomputerized tomography. Matrix metalloproteinase-13 (MMP13) and nitrotyrosine were detected using immunohistochemistry. Administration of GSPE to the MIA-treated rats significantly increased the PWL and PWT and this resulted in recovery of hind paw weight distribution (P < 0.05). GSPE reduced the loss of chondrocytes and proteoglycan, the production of MMP13, nitrotyrosine and IL-1beta and the formation of osteophytes, and it reduced the number of subchondral bone fractures in the MIA-treated rats. These results indicate that GSPE is antinociceptive and it is protective against joint damage in the MIA-treated rat model of OA. GSPE could open up novel avenues for the treatment of OA.