Role of the hepatic function in the development of the pyrogenic tolerance to muramyl dipeptide

We have demonstrated that the hepatic function may have an important role in the development of tolerance to the pyrogenic effect induced by endotoxin. To further investigate if the role of the hepatic function in the development of tolerance also extends to that induced by other pyrogenic stimuli, we investigated the effect of galactosamine, a specific inhibitor of the hepatic protein synthesis, on the development of tolerance to the pyrogenic effect induced by muramyl dipeptide (MDP) in rats. Pyrogenic tolerance was observed after the second intravenous or intraperitoneal injection of MDP (500 microgram/kg), 24 h after the first injection, similar to what was observed with endotoxin. Pyrogenic tolerance was abolished when galactosamine (300 mg/kg ip) was injected simultaneously with MDP (500 microgram/kg iv) on the first day. When uridine (600 mg/kg ip) was administered simultaneously with galactosamine (300 mg/kg ip) and the first injection of MDP (500 microgram/kg ip), pyrogenic tolerance was again observed after the second injection of the peptidoglycan. In conclusion, the hepatic function may not be important only for the development of tolerance to endotoxin, but also to a totally different pyrogenic stimulus such as MDP.     

Thymoquinone attenuates doxorubicin‐cardiotoxicity in rats

Contrary to the fact that doxorubicin is a powerful chemotherapeutic agent for the treatment of neoplastic diseases, cardiotoxicity is too important to be ignored. Thymoquinone serves as a powerful free radical scavenger. In the study, the effects of thymoquinone against doxorubicin‐cardiotoxicity will be evaluated. Forty rats were divided into five groups. Group I: control group (n = 8); group II: olive oil group (n = 8); group III: thymoquinone group (n = 8); given 10 mg/kg thymoquinone intraperitoneally per day throughout the experiment; group IV: doxorubicin group (n = 8); injected with a single dose of 15 mg/kg ip doxorubicin on the 7th day of the experiment; group V: doxorubicin + thymoquinone group (n = 8); administered with 10 mg/kg thymoquinone per day during the experiment and 15 mg/kg doxorubicin ip on the 7th day. The experiment was planned for 14 days. Immunohistochemically, heat shock protein (HSP) 70 and HSP90, glucose‐regulated protein 78 (GRP78), caspase‐3 were stained. We made terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptotic evaluation. Total oxidant status (TOS) levels and total antioxidant status (TAS) were measured in the heart tissue. Atrial natriuretic peptide (ANP) and pro‐B type natriuretic peptide (proBNP) were evaluated. In the study, HSP70, HSP90, GRP78, and caspase‐3 levels increased in group IV. TOS and TAS levels were significant compared to group I. Doxorubicin significantly increased ANP and NT‐proBNP levels. Thymoquinone revealed significant differences in these values. Thymoquinone can be an important cardioprotective agent against doxorubicin‐cardiotoxicity.     

The effect of leptin on adrenal glands in rats with streptozotocin-induced diabetes: an experimental study

OBJECTIVE: To determine the cross-section area of adrenal medulla and the percentage of Ki-67 (a proliferation marker) of the adrenal gland in diabetic rats after leptin injection. STUDY DESIGN: Twenty-nine male Wistar rats were randomly divided into 3 groups: control (C) group (n = 9), diabetes mellitus (DM) group (n = 10) and leptin-injected diabetes mellitus (DM+L) group (n = 10). Experimental DM was induced by a single intraperitoneal dose of streptozotocin (40 mg/kg). After this, leptin (100 microg/kg) was injected subcutaneously for a period of 2 weeks in the diabetic group. RESULTS: An atrophy of adrenal medulla in the DM group was observed, and this atrophy returned to normal morphology after injection of leptin. In addition, an increase in the Ki-67 percentage was demonstrated in the zona reticularis layers in the DM+L group. CONCLUSION: Our study indicated that leptin stimulates the sympathoadrenal system and the androgen producing adrenal cortex in DM rats.     

Effects of pycnogenol treatment on oxidative stress in streptozotocin-induced diabetic rats

Free radicals and oxidative stress have been implicated in the etiology of diabetes and its complications. This in vivo study has examined whether subacute administration of pycnogenol, a French pine bark extract containing procyanidins that have strong antioxidant potential, alters biomarkers of oxidative stress in normal and diabetic rats. Diabetes was induced in female Sprague-Dawley rats by a single injection of streptozotocin (90 mg/kg body weight, ip), resulting (after 30 days) in subnormal body weight, increased serum glucose concentrations, and an increase in liver weight, liver/body weight ratios, total and glycated hemoglobin, and serum aspartate aminotransferase activity. Normal and diabetic rats were treated with pycnogenol (10 mg/kg body weight/day, ip) for 14 days. Pycnogenol treatment significantly reduced blood glucose concentrations in diabetic rats. Biochemical markers for oxidative stress were assessed in the liver, kidney, and heart. Elevated hepatic catalase activity in diabetic rats was restored to normal levels after pycnogenol treatment. Additionally, diabetic rats treated with pycnogenol had significantly elevated levels of reduced glutathione and glutathione redox enzyme activities. The results demonstrate that pycnogenol alters intracellular antioxidant defense mechanisms in streptozotocin-induced diabetic rats.     

Efficiency of propolis extract against mitochondrial stress induced by antineoplasic agents (doxorubicin and vinblastin) in rats

To assess the oxidative stress and mitochondrial dysfunction associated with disease, toxic process and aging, in vivo and in vitro preventive effect of propolis extract against mitochondrial oxidative stress induced by two anticancer drugs (doxorubicin and vinblastin) have been investigated in female wistar rat using liver and heart mitochondria. The results show that doxorubicin and vinblastin altered mitochondrial functions as observed by a decrease in respiratory control value, an activation of swelling and overproduction of superoxide anion. Myocardial tissue from doxorubicin treated rats showed a marked increase in malondialdehyde production, a depletion of reduced glutathione contents and an inhibition of catalase and superoxide dismutase activities. Similar results were also observed in liver tissue. Pretreatment of rats with propolis extract (100 mg/kg/day po) (10(-4) M ip) administered 4 days prior to doxorubicin (20 mg/kg) and/or vinblastin (2 mg/kg) injection, substantially reduced the peroxidative damage in myocardium and hepatic tissues and markedly restored the tissues catalase and SOD activities. The results strongly suggest that propolis extract protects heart and liver tissues from oxidative stress by protecting the mitochondria.     

Greater potency of IGF-I than IGF-I/BP-3 complex in catabolic parenterally fed rats

We compared the anabolic effects of recombinant human insulin-like growth factor I (rhIGF-I, 2.5 mg/kg) and equimolar amounts of rhIGF-I prebound to rhIGF binding protein-3 (rhIGF-I/BP-3) coinfused continuously with total parenteral nutrition (TPN) solution in dexamethasone (Dex, 70 microg/day ip)-treated male rats for 6 days. The four TPN groups included control, Dex, Dex + IGF-I, and Dex+IGF-I/BP-3. Pharmacokinetic analysis indicated reduced clearance of IGF-I when infused as IGF-I/BP-3 compared with free IGF-I (0.91 +/- 0.09 vs. 2.01 +/- 0.19 ml serum/min, P < 0.001) and this was associated with significantly greater serum IGF-I concentrations in the Dex+IGF-I/BP-3 group. Despite greater total serum IGF-I levels, infusion of free IGF-I produced greater anabolic responses than IGF-I/BP-3 based on body weight, nitrogen balance, and jejunal cellularity. Treatment with free IGF-I, but not IGF-I/BP-3, significantly reduced serum insulin and glucose levels that were elevated due to Dex. There were no significant differences in liver IGF-I mRNA levels between groups. Serum IGFBP-3 levels were elevated with infusion of IGF-I/BP-3 compared with IGF-I. These results indicate greater anabolic potency of IGF-I compared with IGF-I/BP-3 when administered by continuous parenteral infusion with TPN solution in catabolic rats.     

Effects of maternal leptin treatment during lactation on the body weight and leptin resistance of adult offspring

We investigate whether leptin treatment to lactating rats affects food intake, body weight and leptin serum concentration and its anorectic effect on their adult offspring. Lactating rats were divided into 2 groups: Lep-single injected with recombinant rat leptin (8 microg/100 g of body weight, daily for the last 3 consecutive days of lactation) and control group (C) that received the same volume of saline. After weaning all pups had free access to the control diet, their body weight and food intake were monitored at each 4 days until 180 days of age, when they were tested for its food intake and response to either leptin (0.5 mg/kg body wt, ip) or saline vehicle. The offspring of the leptin-treated dams gained more weight and had higher food intake from day 37 onward (p<0.05), higher amount of retroperitoneal white adipose tissue (RPWAT) (37%, p<0.05) and higher leptin serum concentration (40%, p<0.05) at 180 days of age compared to control group. The food intake at 2, 4, 6 and 24 h was unaffected after acute injection of leptin in these animals, suggesting resistance to the anorectic effect of leptin. The maternal leptin treatment during lactation makes their adult offspring more susceptible to overweight with resistance to the anorectic effect of leptin.     

S100A1 as a Potential Diagnostic Biomarker for Assessing Cardiotoxicity and Implications for the Chemotherapy of Certain Cancers

This study examined the value of blood marker S100A1 in detecting cardiotoxicity induced by chemotherapy agents; trastuzumab and lapatinib, in normal rat heart. The rats were divided into three groups: control (n = 8, no treatment), T (n = 8, one time ip treatment with 10 mg/kg trastuzumab) and L (n = 8, oral treatment with 100 mg/kg/day lapatinib for 7 days). The activities of oxidative stress parameters Malondialdehyde (MDA), Superoxide dismutase (SOD), Catalase (CAT) and Glutathione (GSH) were measured from the extracted cardiac tissues. The levels of troponinI and S100A1 expressions were measured from blood samples. All biomarkers responded to the treatments as they exhibited alterations from their normative values, validating the chemically induced cardiotoxicity. S100A1 expression attenuated significantly (75%), which made the sensitive detection of cardiotoxicity feasible. Assessment of cardiotoxicity with S100A1 may be a valuable alternative in clinical oncology of cancers in some organs such as breast and prostate, as they do not overexpress it to compete against.     

Troglitazone can prevent development of type 1 diabetes induced by multiple low-dose streptozotocin in mice.

Recent investigations suggest that cytotoxic cytokines such as tumor necrosis factor (TNF)alpha and interleukin (IL)-1beta or free radicals play an essential role in destruction of pancreatic beta cells in Type 1 diabetes and that, therefore, anti-oxidant or anti-TNF alpha and IL-1beta therapy could prevent the development of Type I diabetes. Troglitazone belongs to a novel class of antidiabetic agent possessing the ability to enhance insulin action provably through activating PPAR gamma and to scavenge free radicals. In the present study, we examined whether troglitazone can prevent the development of Type 1 diabetes in multiple, low-dose streptozotocin (MLDSTZ)-injected mice. In addition, effects of troglitazone on cytokine-induced pancreatic beta cell damage were examined in vitro. Type 1 diabetes was induced by MLDSTZ injection to DBA/2 mice (40 mg/kg/day for 5 days). Troglitazone was administered as a 0.2% food admixture (240 mg/kg/day) for 4 weeks from the start of or immediately after STZ injection. MLDSTZ injection elevated plasma glucose to 615 +/- 8 mg/dl 4 weeks after final STZ injection and was accompanied by infiltration of leukocytes to pancreatic islets (insulitis). Troglitazone treatment with MLDSTZ injection prevented hyperglycemia (230 +/- 30 mg/dl) and, suppressed insulitis and TNF alpha production from intraperitoneal exudate cells. TNF alpha (10 pg/ml) and IL-1beta (1 pg/ml) addition to hamster insulinoma cell line HIT-T15 for 7 days in vitro decreased insulin secretion and cell viability. Simultaneous troglitazone addition (0.03 to approximately 3 microM) significantly improved cytokine-induced decrease in insulin secretion and in cell viability. These findings suggest that troglitazone prevents the development of Type 1 diabetes in the MLDSTZ model by suppressing insulitis associated with decreasing TNF alpha production from intraperitoneal exudate cells and the subsequent TNF alpha and IL-1beta-induced beta cell damage.     

Inhibition of both the apical sodium-dependent bile acid transporter and HMG-CoA reductase markedly enhances the clearance of LDL apoB

Discovery of the ileal apical sodium-dependent bile acid transporter (ASBT) permitted development of specific inhibitors of bile acid reabsorption, potentially a new class of cholesterol-lowering agents. In the present study, we tested the hypothesis that combining the novel ASBT inhibitor, SC-435, with the HMG-CoA reductase inhibitor, atorvastatin, would potentiate reductions in LDL cholesterol (LDL-C) and LDL apolipoprotein B (apoB). ApoB kinetic studies were performed in miniature pigs fed a typical human diet and treated with the combination of SC-435 (5 mg/kg/day) plus atorvastatin (3 mg/kg/day) (SC-435+A) or a placebo. SC-435+A decreased plasma total cholesterol by 23% and LDL-C by 40%. Multicompartmental analysis (SAAM II) demonstrated that LDL apoB significantly decreased by 35% due primarily to a 45% increase in the LDL apoB fractional catabolic rate (FCR). SC-435+A significantly decreased hepatic concentrations of free cholesterol and cholesteryl ester, and increased hepatic LDL receptor mRNA consequent to increased cholesterol 7alpha-hydroxylase expression and activity. In comparison, SC-435 (10 mg/kg/day) monotherapy decreased LDL apoB by 10% due entirely to an 18% increase in LDL apoB FCR, whereas atorvastatin monotherapy (3 mg/kg/day) decreased LDL apoB by 30% due primarily to a 22% reduction in LDL apoB production. We conclude that SC-435+A potentiates the reduction of LDL-C and LDL apoB due to complementary mechanisms of action.     

Comparative effectiveness of CaNa3DTPA and tiron along with alpha-tocopherol against beryllium-induced biochemical alterations in rats

The therapeutic efficacy of chelating agents CaNa3DTPA (calcium trisodium diethylene triamine penta acetic acid) and Tiron (sodium-4,5-dihydroxy-1,3-benzene disulphonate) with and without antioxidant, alpha-Tocopherol was evaluated in the treatment of beryllium-induced toxicity in female albino rats. The animals were exposed to beryllium (as beryllium nitrate) at a dose of 1 mg/kg (ip) once a day for 28 consecutive days followed by chelation therapy by CaNa3DTPA (0.1 mM/kg, ip) and Tiron (471 mg/kg, ip) with and without alpha-Tocopherol (25 mg/kg, orally) for 5 consecutive days after toxicant administration. Tissue biochemistry revealed severe alterations in liver and kidney. A significant fall in total protein and glycogen contents, alkaline phosphatase, adenosine tri-phosphatase and succinic dehydrogenase level was noticed. On the contrary, an elevation in acid phosphatase was recorded. The significant rise in hepatic lipid peroxidation and decreased level of hepatic reduced glutathione showed toxicity due to beryllium. CaNa3DTPA with alpha-Tocopherol showed moderate therapeutic efficacy while Tiron in combination with alpha-Tocopherol exerted statistically more beneficial effects to reverse biochemical alterations in different variables altered due to beryllium intoxication.     

Ameliorative Effect of Carvacrol on Cisplatin‐Induced Reproductive Damage in Male Rats

Cisplatin (CP) treatment causes the damage in male reproductive system. Carvacrol (CARV) is an antioxidant that is naturally found in some plants. We aimed to investigate the effect of CARV on CP‐induced reproductive toxicity in male rats. Eighteen adult male Sprague–Dawley rats were used. The control group (n = 6) was treated orally with physiological saline (PS) daily for 14 days and a single intraperitoneal (IP) PS injection on day 10. The CP group (n = 6) was administered with daily oral PS for 14 days and a single IP injection of 10 mg/kg CP on day 10. The CARV + CP group (n = 6) was treated with daily 75 mg/kg oral CARV for 14 days and a single IP injection of 10 mg/kg CP on day 10. CP treatment caused the damage on some spermatological parameters (motility, live sperm rate, and abnormal sperm rate), increased the oxidative stress, and induced testicular degeneration and apoptosis. However, CARV treatment mitigates CP‐induced reproductive toxicity.     

Hormonal Regulation of Leptin mRNA Expression and Preadipocyte Recruitment and Differentiation in Porcine Primary Cultures of S-V Cells

The hormonal regulation of leptin mRNA expression and the association between leptin expression and adipocyte differentiation were examined in primary cultures of porcine S-V cells with Northern blot and immunocytochemical analysis. Seeding for 3 days with fetal bovine serum (FBS) with varying levels of dexamethasone (Dex) increased levels of leptin mRNA in a dosedependent manner in parallel with increases in the proportion of preadipocytes (AD-3 positive cells; AD-3, a preadipocyte marker). Six-day treatment with 10 or 850 nM insulin after FBS+Dex treatment resulted in a similar increase in leptin mRNA expression and morphological differentiation. However, significantly lower levels of leptin mRNA and smaller fat cells were observed in cultures treated with 1 nM insulin or 10 nM insulin-like growth factor-I (IGF-I). Dex-induced increases in leptin mRNA levels and AD-3 cell numbers were blocked completely by the addition of transforming growth factor-β (TGF-β) to FBS+Dex-treated cultures. However TGF-β significantly increased fat cell size and leptin mRNA expression when added to ITS (insulin, 850 nM; transferrin, 5 μg/ml; and selenium, 5 ug/mL) treated cultures during the lipid-filling stage. When added with FBS+DEX for the first 3 days, growth hormone (GH) did not influence the Dex-induced increase in AD-3 cells and leptin mRNA expression, but GH reduced leptin mRNA levels when added with insulin for 6 days after FBS+Dex. These results demonstrated that regulation of leptin mRNA expression by Dex, insulin, IGF-I, TGF-β, and GH may be associated with changes in preadipocyte number and fat cell size.     

Klotho Suppresses Cardiomyocyte Apoptosis in Mice with Stress-Induced Cardiac Injury via Downregulation of Endoplasmic Reticulum Stress

Cardiomyocyte apoptosis is a common pathological alteration in heart disease which results in systolic dysfunction or sudden death. Klotho is a novel anti-aging hormone. We tested the effects of klotho on cell apoptosis in isoproterenol-treated cardiomyocytes. In BALB/c mice, cardiac injury was induced by subcutaneous injection of isoproterenol (5mg/kg, for 9days, sc). Klotho (0.01 mg/kg, every other day for 4days, ip) was administered to determine the changes in isoproterenol-induced apoptosis. Mouse heart was harvested at day 2, day 5, and day 9 after isoproterenol injection. Isoproterenol induced cardiac apoptosis and endoplasmic reticulum (ER) stress in a time-dependent manner. However, klotho partly reversed isoproterenol-induced cardiac apoptosis and ER stress. These same effects were observed in cultured cardiomyocytes. Furthermore, the results also showed that SB203580, a p38 inhibitor, and SP600125, a c-Jun NH2-terminal kinase (JNK) inhibitor, reduced cardiomyocyte apoptosis and ER stress, however, klotho suppressed isoproterenol-induced activation of p38 and JNK. Taken together, these results indicated that cardioprotection by klotho was related to the attenuation of ER stress and ER stress-induced apoptosis, at least partly, through suppressing activation of the p38 and JNK pathway.     

姜黄素对小鼠胆汁淤积性肝纤维化的改善作用及其机制研究*

目的:探讨姜黄素对小鼠胆管结扎所致的胆汁淤积性肝纤维化的保护作用,为肝纤维化治疗提供新的治疗方法。方法:42只健康成年雄性BALB/c小鼠随机分为假手术(n=6)处理组、假手术+姜黄素(n=6)处理组、胆管结扎(BDL)处理组(n=10)、BDL+姜黄素处理组(n=10),BDL+姜黄素+锌原卟啉(ZnPP)处理组(n=10)。BDL手术7 d后,假手术+姜黄素组、BDL+姜黄素组每日给予姜黄素(30 mg / kg)腹腔注射;BDL+姜黄素+ZnPP组每日给予姜黄素(30 mg / kg)以及nPP(50 μmol/ kg)腹腔注射;对于假手术组和BDL组,小鼠每天一次腹膜内注射等体积的盐水。整个给药过程持续7 d。小鼠BDL14 d后,取血和肝脏组织,检测谷草转氨酶(AST)、谷丙转氨酶(ALT)水平,观察肝组织病理形态变化、肝纤维化情况、检测肝组织中血红素加氧酶-1(HO-1)的蛋白表达。结果:与假手术组相比,BDL组小鼠肝脏胆囊肿大,血清谷草转氨酶(ALT)、谷丙转氨酶(AST)水平显著升高 (P＜0.05),同时,天狼星红染色及促纤维化相关基因的qRT-PCR结果显示肝脏出现胶原蛋白沉积,巨噬细胞及中性粒细胞免疫组化结果显示肝脏出现炎性细胞浸润;与BDL组相比,姜黄素治疗组血清ALT、AST水平明显降低(P＜0.05),胶原蛋白沉积及炎性细胞浸润情况有所改善,同时,补充姜黄素后HO-1表达升高(P＜0.05);对姜黄素治疗组给予HO-1活性抑制剂ZnPP发现,姜黄素对肝损伤的保护作用被逆转。结论:姜黄素可以改善BDL所致的肝脏炎症及肝纤维化,这种保护作用可能与姜黄素调节HO-1活性有关。     

The irreversible binding of benzo[a]pyrene to rat liver macromolecules in vivo and in vitro: effects of agents that influence benzo[a]pyrene metabolism

The present study was carried out to determine the effects of agents that influence benzo[a]pyrene (BP) metabolism in vitro on the irreversible binding of BP to rat hepatic macromolecules in vivo. The irreversible binding of [3H]BP was found to be both dose and time dependent after its intraperitoneal administration to male Wistar rats. The SKF 525-A, at doses of 50 and 75 mg/kg, ip 3 h before BP, decreased the level of binding from control by 31 and 34%, respectively. At 35 mg/kg, SKF-525-A had no effect. Diethyl maleate (0.6 mL/kg, ip) and cysteine (150 mg/kg, ip), 30 and 5 min before BP, respectively, did not alter the binding of BP from control. Oral methadone treatment, previously shown to increase selectively epoxide hydrase activity in male Wistar rats, also failed to alter the amount of BP bound to hepatic macromolecules. 3-Methylcholanthrene (20 mg/kg per day, ip, for 2 days) administered 24 h before BP, decreased the level of binding from control by 30%. Parallel in vitro studies were carried out with the various agents used in vivo.     

Neural, pituitary, and mammary tumors in Sprague-Dawley rats treated with X irradiation to the head and N-Ethyl-N-nitrosourea (ENU) during the early postnatal period: a statistical study of tumor incidence and survival

To study the late effects of early postnatal treatment with N-ethyl-N-nitrosourea (ENU) preceded by X irradiation to the head, 226 neonatal CD rats were divided into six groups which received the following treatment: (1) 500-rad X irradiation to the head on the third postnatal day (pnd); (2) injection ip with 30 mg/kg ENU on the fourth pnd; (3) injection ip with 30 mg/kg ENU on the seventh pnd; (4) a combination of 500-rad X irradiation to the head on the third pnd, followed by ip 30 mg/kg ENU on the fourth pnd; (5) a combination of 500-rad X irradiation to the head on the third pnd, followed by ip 30 mg/kg ENU on the seventh pnd; and (6) untreated controls. The results indicate that (1) X irradiation to the head alone significantly extended the life span of females compared to that of control females, and did not affect survival of males; (2) X irradiation did not influence the latent period or mortality from neurogenic tumors when ENU was given 1 or 3 days afterward; (3) ENU itself was a factor in shortening latent periods for mammary tumors; (4) X irradiation alone did not increase the incidence of mammary tumors, and revealed no protective effect on the ENU-induced mammary carcinogenesis; (5) X irradiation increased the prevalence of pituitary tumors in the females; (6) no enhancement of pituitary tumors by ENU was observed: and (7) there was a statistically significant association of pituitary and mammary tumors in females.     

Dealkylation of pentoxyresorufin: A rapid and sensitive assay for measuring induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat

The O-dealkylation of pentoxyresorufin (7-pentoxyphenoxazone) by rat liver microsomes was examined. The reaction appeared highly specific for certain phenobarbital inducible forms of cytochrome P-450 and was increased 95- to 140-fold by animal pretreatment with phenobarbital (75 mg/kg/day, four ip injections) and ~50-fold by Aroclor 1254 (500 mg/kg, one ip injection) while animal pretreatment with 3-methylcholanthrene (50 mg/kg/day, three ip injections) resulted in less than a 2-fold increase over the rate detected in control microsomes. It was observed that this activity, in microsomes for Aroclor-pretreated rats, was dependent on O₂ and was inhibited by metyrapone and SKF 525-A, indicative of cytochrome(s) P-450 mediation in the reaction. When antibodies directed against purified cytochrome(s) P-450S were employed to inhibit the pentoxyresorufin O-dealkylation reaction, antibodies to P-450_PB-B greatly inhibited the reaction (>90%), while antibodies to P-450_PB-C or P-450_PB/PCN-E had minimal effects. Assay of hepatic microsomes from rats which were pretreated with varying doses of phenobarbital (0.9–75 mg/kg/day, four ip injections) indicated that while aminopyrine-N-demethylase activity was induced only 2-fold at the maximum dose (75 mg/kg/day), pentoxyresorufin O-dealkylase activity was induced ~140-fold at this dose and ~4-fold by a dose of phenobarbital as low as 0.9 mg/kg.     

Palliative effect of curcumin on doxorubicin‐induced testicular damage in male rats

This study aimed to investigate the effect of curcumin (CUR) on doxorubicin (DOX)‐induced testicular damage in male rats. Thirty‐five adult male Wistar rats were used. Control group was received saline for 7 days. CUR group received CUR for 7 days. DOX group received single dose DOX on the 5th day. DOX+ CUR‐100 group received 100 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX + CUR‐200 group received 200 mg/kg/day CUR for 7 days and DOX injection on the 5th day. DOX treatment decreased in sperm motility rate, live sperm percentages, cellular antioxidants, and increased malondialdehyde (MDA) levels, necrosis, degenerations, and slimming in seminiferous tubules, and DNA damages in testes by inducing oxidative stress. CUR treatment mitigated significantly these side effects when compared with DOX group in a dose‐dependent manner. In conclusion, CUR treatment can be used in the mitigation of DOX‐induced testicular toxicity.     

Studies on the embryotoxicity and mutagenicity of mycotoxins

Embryotoxicity: Aflatoxin B₁(AFB₁), G₁ (AFG₁), and Patulin (PA) were investigated in NMRI mice for embryotoxic and teratogenic activity. These three mycotoxins were injected intraperitoneally or given orally on day 12 and 13 of pregnancy. AFB₁ (15, 45, and 90 mg/kg ip or 45 mg/kg po) produced a moderate retardation in the fetal development and a dose related increase of cleft palates, wavy ribs, and diaphragm changes. The effects after injection of AFG₁ (45 and 90 mg/kg ip) were reduction of fetal weights, increase of diaphragm changes, and malformations of kidneys. PA (1.25, 2.5, and 3.75 mg/kg ip or 3.75 mg/kg po) elevated the rate of cleft palates after 3.75mg/kg. In the dominant lethal assay neither PA (2.5 and 5 mg/kg ip) nor AFB₁) (15 and 45 mg/kg ip) increased the frequency of the dominant lethal mutations. Both mycotoxins showed no mutagenic activity in this test system. The capability of AFB₁, AFG₁, and PA to induce chromosome damages in vivo was tested in the Chinese Hamster by examination of bone marrow cells, each after two oral doses (AFB₁: 12.5 and 25 mg/kg; 25 and 50 mg/kg; PA: 10 and 20 mg/kg). The three mycotoxins induced chromosome aberrations in the following order of activity: PA > AFB₁ > AFG₁.