HYPOTHYROIDISM INCREASES EXPRESSION OF STERILE INFLAMMATION PROTEINS IN RAT HEART TISSUE.

PURPOSE: In this study, we aimed to investigate the relationship between hypothyroidism and sterile inflammation in rat heart tissue. METHODS: Groups; control group (fed with standard rat chow diet and tab water) and the hypothyroid group (fed with a standard rat chow diet and tap water containing 0.05% 6-n-propyl-2-thiouracil for 6-weeks). At the end of the experiment, histopathologic examination was performed. The T3, T4, TSH and myocardial malondialdehyde (MDA) measurements were performed with an ELISA kit. TUNEL assay was performed to demonstrate apoptosis. Sterile inflammation markers, caspase-1 and NLRP3, were investigated by immunohistochemistry and western blot. RESULTS: In histopathological examination, we observed leukocyte infiltration, myocardial atrophy, pyknotic nucleated cells and cytoplasmic vacuolization in hypothyroid group whereas the control group showed normal structure. MDA levels in myocardial tissue were significantly high in hypothyroid group when compared to the control group (P<0.05). Myocardial apoptosis increased in hypothyroid group when compared to the control group. NLRP3 and caspase-1 immunoreactivity was higher in the hypothyroid group. In ELISA results, we found significantly higher level of TSH and lower levels of T3 and T4 in hypothyroid group when compared to the control group. CONCLUSION: Hypothyroidism increased oxidative stress, and caused inflammatory alterations in cardiac tissue. In addition, our study also suggested that thyroid hormone deficiency would increase the amounts of cardiac NLRP3 and caspase-1 protein, which indicates that hypothyroidism exerts its destructive effects through sterile inflammation. Elucidation of sterile inflammation-associated pathways may produce promising results in the treatment of hypothyroidism-induced cardiac damage.

Chitosan gel formulations containing egg yolk oil and epidermal growth factor for dermal burn treatment.

In the present study chitosan based gel formulations containing Egg Yolk Oil (EYO) and Epidermal Growth Factor (EGF) were formulated successfully aiming at enhanced topical treatment of dermal burns the combination of traditional approaches with modern drug delivery systems. Physicochemical properties of the formulations were analyzed and efficacy of the formulations prepared were evaluated versus a commercial product; Silverdin (1% silver sulfadiazine) in vivo on Wistar rats. Burns were generated on the back of the rats and at predetermined time intervals tissue samples were collected and evaluated histologically. The analyses showed that chitosan based gel formulations containing Egg Yolk Oil (E1) and chitosan based gel formulations containing EYO and EGF (M1) formulations seem to be better alternatives for Silverdin with a significant difference (p < 0.05) considering healing ranks of tissue samples.

Ethanol-induced hepatotoxicity and protective effect of betaine.

The protective effects of betaine in ethanol hepatotoxicity were investigated in 24 female wistar albino rats. Animals were divided into three groups: control, ethanol and ethanol + betaine group. Animals were fed liquid diets and consumed approximately 60 diet per day. Rats were fed ethanol 8 kg(- 1) day(- 1). The ethanol + betaine group were fed ethanol plus betaine (0.5% w/v). All animal were fed for 2 months. Reduced glutathione, malondialdehyde and vitamin A were determined in the liver tissue. Alanine aminotransferase activities were also measured on intracardiac blood samples. GSH levels in the ethanol group were significantly lower than these in the control group (p < 0.001). GSH was elevated in the betaine group as compared to the ethanol group (p < 0.001). MDA in the ethanol group was significantly higher than that in the control group (p < 0.05). MDA was decreased in the betaine group as compared to the ethanol group (p < 0.05). Vitamin A in the ethanol group was significantly lower than that in the control group (p < 0.01), but, in the ethanol + betaine group it was high compared with the ethanol group (p < 0.01). ALT in the ethanol group was higher than that in the control group (p < 0.05). Oxidative stress may play a major role in the ethanol-mediated hepatotoxicity. Betaine may protect liver against injury and it may prevent vitamin A depletion. Therefore, it may be a useful nutritional agent in the prevention of clinical problems dependent on ethanol-induced vitamin A depletion and peroxidative injury in liver.

Non-hindbrain-related syringomyelia. Obstruction of the subarachnoid space and the central canal in rats. An experimental study.

BACKGROUND: The aim is to determine the mechanism of non-hindbrain-related syringomyelia in experimental models. The effects of obstruction of central canal and subarachnoid space on occurrence of cavities were discussed. METHODS: 31 Sprague-Dawley rats were used with eight (Group D) as a control. In 10 rats (Group A) 1.5 microl kaolin was microinjected into the dorsal columns and central gray matter of the spinal cord at the level of Th6-10. In 10 rats (Group B) 0.1 cc kaolin was injected into the subarachnoid space at the same level. In 3 rats (Group C), 1.5 microl kaolin was administered into both dorsal midline of the spinal cord and the subarachnoid space. RESULTS: In Group A, histological examination revealed cystic cavity and dilatation of the central canal in five rats; denuded ependymal line and multicystic formations in ependymal and periependymal areas in seven rats. In Group B, denuded ependymal line in three rats and microcystic formations in ependymal and periependymal areas in four rats were revealed. In Group C, there were microcystic formations in two rats and syrinx cavity in one rat. CONCLUSIONS: Developments leading to occurrence of cavities are focused on the central canal in all groups. These models indicate that the CSF-flow is from the subarachnoid space to the central canal leading to changes of cavities. In cases of obstruction of the subarachnoid space or the central canal, the occurrence of syrinx cavity initially is due to increased CSF (cerebrospinal fluid) pressure in the central canal. Flow changes in spinal cord is indicated by this study.

The role of free radicals in p-aminophenol-induced nephrotoxicity: does reduced glutathione have a protective effect?

The role of free radicals in p-aminophenol (PAP)-induced nephrotoxicity and effects of reduced glutathione (GSH) were investigated. We injected PAP in one group of rats and PAP plus GSH in a second group. All parameters were measured in the renal tissue. Superoxide dismutase (SOD) activity in the PAP + GSH group (7.1 +/- 0.36 U/mg protein) was found to be significantly higher than in the control group (4.9 +/- 0.13) (P < 0.001). Catalase (CAT) was found to be significantly low in both groups (P < 0.001 in the PAP group (13.48 +/- 0.85 U/mg protein), P < 0.01 in the PAP + GSH group (18.75 +/- 1.17) as compared to the control group (41.03 +/- 0.93)). Glutathione peroxidase (GPx) in the PAP and PAP + GSH groups was found to be significantly high (P < 0.01 in the PAP group (5.32 +/- 0.033 U/mg protein), P < 0.001 in the PAP + GSH group (6.48 +/- 0.1)) as compared to the control group (2.93 +/- 0.093)). Similarly, glutathione reductase (GSSGR) in the PAP (0.023 +/- 0.002 U/mg protein), and PAP + GSH (0.025 +/- 0.001) groups was found to be significantly high as compared to the control group (0.014 +/- 0.001) (P < 0.001). GSH in the PAP (161.93 +/- 8.3 mg/mg protein) and PAP + GSH (170.7 +/- 4.51) groups were found to be significantly higher than the control group (104.91 +/- 3.0) (P < 0.001). Malondialdehyte (MDA) in the PAP (11.2 +/- 0.62 nmol/mg protein) and PAP + GSH (9.72 +/- 0.46) groups was found to be significantly higher than in the control group (5.54 +/- 0.51)(P < 0.001). Free radicals might have a major role in the PAP-induced nephrotoxicity. GSH increased nephrotoxicity.

The effect of vasoactive intestinal peptide (VIP) on mast cell invasion/degranulation in testicular interstitium of immobilized + cold stressed and beta-endorphin-treated rats.

The effect of VIP on mast cell invasion/degranulation in testicular interstitium of stressed (immobilization and cold) and beta-endorphin-treated rats were investigated. Fifty-three Wistar male rats were used in four series of experiments. Initially, the effect of immobilization and cold stress on mast cell invasion and degranulation in testicular interstitium was examined in three age group of rats: 15 (n = 6), 30 (n = 6), and 45 (n = 7) days of age. Five animals per age group were used as controls. Because the most obvious effect of the stress on mast cell invasion/degranulation in testicular interstitium was observed in 45-day-old rats, the action of VIP in stressed and beta-endorphin-treated rats was only investigated at this age group. Mast cells and Leydig cells were evaluated by using histochemical and light microscopic protocols. Stress caused mast cell accumulation and degranulation in the testicular interstitium. Stress decreased heparin synthesis and possibly increased histamine content of mast cells. The effect of beta-endorphin was not as high as seen with stress. In some areas of testicular interstitium of stressed rats, there were aplasic and/or inactive Leydig cells. VIP inhibited proliferation and degranulation of mast cells, increased heparin content of the cells, and protected Leydig cells. By way of mast cell accumulation and degranulation in the testicular interstitium, exposure to stress may lead to Leydig cell damage and infertility. VIP may be involved in the protection of normal testicular function under stress conditions.

Oxygen-free radicals impair fracture healing in rats.

We studied the effect of oxygen-free radicals on fracture healing. 30 male rats were divided into 2 groups: 15 rats were given saline 5 mL/kg i.p. (control group) and 15 were given zymosan 100 mg/kg i.p. to induce oxygen-free radicals through stimulation of NADPH oxidase in polymorphonuclear leucocytes. 1 hour later, the right forelimbs of the rats were broken by light manual compression. These treatments were given once a day until the fifth post-fracture day. All rats were killed on day 22, and histological sections of the radius and ulna were examined without knowledge of the treatment given. The administration of zymosan impaired the fracture healing and therefore oxygen-free radicals appear to play an important role in fracture healing.

Mast cell degranulation in hemorrhagic shock in rats and the effects of vasoactive intestinal peptide, aprotinin and H1 and H2-receptor blockers on degranulation.

Various stressful stimuli cause mast cell degranulation. Hemorrhagic shock is one such stressful stimulus which may cause mast cell degranulation and histamine release. Histamine may be involved in the pathophysiology of hemorrhage. It was reported that there are large amounts of histamine in the anterior and posterior lobes of the pituitary and the adjacent median eminence of the hypothalamus. Most of the histamine in the posterior pituitary is in mast cells. In addition, both vasoactive intestinal peptide (VIP) and histamine-containing neurons are available in the hypothalamus. It therefore seems reasonable to suppose that these three systems (i.e., mast cells, VIP-containing neurons, and histamine-containing neurons) may play an important role in the progression of hemorrhagic shock. 66 albino rats (200-250 g) of either sex were used. The presence of mast cells was examined by light microscopy. Hemorrhage caused mast cell degranulation in a correlation with the amount of blood loss. In all cases, the most intense degranulation was observed in the hypothalamus, especially the nucleus arcuatus, and in the subcutaneous tissue. The intensity of degranulation gradually decreased in the peripheral blood vessel, peritoneum and omentum, in this order. VIP prevented degranulation, but aprotinin and H1 and H2 receptor blockers did not.

Effects of various acidic and alkaline solutions used to dissolve urinary calculi on the rabbit urothelium.

It is well known that infection-induced stones (apatite, struvite), uric acid and cystine calculi in the urinary tract can be managed by the use of certain chemical solutions. We investigated the effects of various acidic and alkaline solutions on the rabbit urothelium. Acidic solutions (pH: 4.2) caused more urothelial injury as compared to alkaline solutions (pH: 7.6). Ureteral injury was more severe than the bladder injury. Magnesium-containing solutions caused less injury to the urothelium.