Population distribution profiles of the activities of blood alanine and aspartate aminotransferase in the normal F344 inbred rat by age and sex

Data on the blood enzyme activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were collected from control male and female F344 rats participating in toxicity studies at 17, 30, 56, 80 and 106 weeks of age. The data were skewed to the right with significant deviation from normality. Applying the Box-Cox transformation, it was concluded that approximately normal distributions could be obtained by using the reciprocal transformation. In general, the males showed a greater degree of heterogeneity for both enzymes. Enzyme activities at 17 weeks were lowest for both ALT and AST. There was a high correlation between the activities of blood ALT and AST, with some animals showing dramatic transient increases. Significant differences among studies with respect to the enzyme activities in rats of the same age were demonstrated.     

Comparative evaluation of hepatotoxic and nephrotoxic effects of aroclors 1221 and 1254 in female rats

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants. This study compared effects of two PCB mixtures, Aroclors 1221 (A1221) and 1254 (A1254) on serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), urea, creatinine and uric acid in female rats. Histopathological changes in the liver and kidney were also examined. A group of adult Wistar rats served as controls. Groups II and III were subcutaneously injected with A1221 and A1254 at 10 mg/kg every other day for 6 weeks. At the end of this period, all animals were decapitated and blood samples were collected. Serum urea, creatinine, uric acid, ALT, AST and ALP levels were determined. Liver and kidney were collected for histopathological examination. They were fixed in formaldehyde and processed for light microscopy. Both A1221 and 1254 significantly elevated serum ALT (p < 0.05) and AST (p < 0.01) levels compared to the control group. Serum ALP values were significantly increased by A1221 (p < 0.05), but they were unaffected in the A1254 group. Treatment with both A1221 and A1254 significantly increased serum levels of urea (p < 0.05), creatinine (p < 0.01) and uric acid (except in the A1221 group; p < 0.005). Distinct histopathological changes including renal corpuscular atrophy, peritubular vascular congestion and dilated cortical tubules, sinusoidal dilatation, congestion and mononuclear cell infiltration were observed. These findings suggest that PCBs may cause nephrotoxicity and hepatotoxicity in female rats.     

Sex- and age-specific clinical and immunological features of coronavirus disease 2019

To simultaneously determine clinical and immunological responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in young and old females and males, 681 coronavirus disease 2019 (COVID-19) patients and 369 normal controls (NCs) were analyzed based on age and sex classifications using multiple linear regression analysis. Compared to the age-matched NCs, both young and old male and female non-comorbid COVID-19 patients had lower lymphocyte counts and alanine aminotransferase (ALT) concentration, and only young male and female patients had lower neutrophil counts. Compared to young patients, both old males and females had significantly higher plasma ALT and AST concentrations. Compared to young and old females, age-matched males had higher plasma ALT and AST concentrations, but only young males had higher C-reactive protein (CRP) concentration. Compared to females, old males, but not young males, showed higher incidence of critical illness. Compared to young patients, old females had more leukocyte and neutrophil counts above the normal upper limit and B cell count below the normal lower limit (NLL), while old males had more lymphocyte and natural killer (NK) cell counts below the NLL. No sex or age associations with B cell and NK cell counts were observed. However, there were age-dependent decreases in CD8⁺ T-cell counts in both male and female COVID-19 patients. Age was negatively associated with CD8⁺ T cell counts but positively associated with neutrophil count, CRP, ALT, and AST concentrations, and sex (females) was negatively associated with neutrophil count, CRP, ALT, and AST concentrations. The present study suggests that SARS-CoV-2 infection mainly induced 1) beneficial sex (female)-related differences regarding reduced COVID-19 disease severity and negative associations with inflammatory responses and liver damage, and 2) harmful age-related differences relating to negative associations with CD8⁺ T cell count and positive associations with inflammatory responses and liver damage. Thus, sex and age are biological variables that should be considered in the prevention and treatment of COVID-19.     

Liver iron overload induced by tamoxifen in diabetic and non-diabetic female Wistar rats

Tamoxifen (TX), a drug used in the treatment of breast cancer, may cause hepatic changes in some patients. The consequences of its use on the liver tissues of rats with or without diabetes mellitus (DM) have not been fully explored. The purpose of this study was to evaluate the correlation between plasma hepatic enzyme levels and the presence of iron overload in the hepatic tissue of female Wistar rats with or without streptozotocin-induced DM and using TX. Female rats were studied in control groups: C-0 (non-drug users), C-V (sorbitol vehicle only) and C-TX (using TX). DM (diabetic non-drug users) and DM-TX (diabetics using TX) were the test groups. Sixty days after induced DM, blood samples were collected for glucose, alanine aminotransferase (ALT), aspartate aminotransferase (AST) alkaline phosphatase (ALP) and bilirubin measures. Hepatic fragments were processed and stained with hematoxylin and eosin, Masson’s trichrome, Perls. The hepatic iron content was quantified by atomic absorption spectrometry. AST, ALT and ALP levels were significantly elevated in the DM and DM-TX groups, with unchanged bilirubin levels. Liver iron overload using Perls stain and atomic absorption spectrometry were observed exclusively in groups C-TX and DM-TX. There was positive correlation between AST, ALT and ALP levels and microscopic hepatic siderosis intensity in group DM-TX. In conclusion, TX administration is associated with liver siderosis in diabetic and non-diabetic rats. In addition, TX induced liver iron overload with unaltered hepatic function in non-diabetic rats and may be a useful tool for investigating the biological control of iron metabolism.     

Effects of melatonin on carbon tetrachloride-induced changes in rat serum

Carbon tetrachloride (CCl4) is a volatile organic chemical, which causes tissue damage, especially to the liver and kidney. In experimental animals it has been shown to be carcinogenic. This study was designed to evaluate the effects of exogenous melatonin administration on the CCl4-induced changes of some biochemical parameters in rat blood. Twenty-four male Wistar rats were randomly divided into three equal groups: Control, CCl4 and CCl4 plus melatonin (CCl4+MEL). Rats in CCl4 group were injected subcutaneously with CCl4 0.5 ml/kg in olive oil while rats in CCl4+MEL group were injected with CCl4 (0.5 ml/kg) plus melatonin (25 mg/kg in 10% ethanol) every other day for one month. Control rats were treated with olive oil. Serum urea, creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), total iron, and magnesium levels were determined. Serum AST, ALT, total and conjugated bilirubin, ALP, gamma-GT, and total iron levels were significantly higher in CCl4-treated rats than in the controls, while urea, total protein, and albumin levels were significantly lower. Melatonin treatment did not cause a significantly change in serum urea, total protein, and albumin levels. However, the elevations in AST, ALT, total and conjugated bilirubin, ALP, gamma-GT, and total iron levels induced by CCl4 injections were significantly reduced by melatonin. On the other hand, melatonin administration significantly decreased serum magnesium levels. These results indicate that melatonin could be a protective agent against the CCl4 toxicity in rats, most likely through its antioxidant and free radical scavenger effects.     

Differential effects of two estrogen antagonists on the development of masculine and feminine sexual behavior in hamsters

To determine whether nonsteroidal antiestrogens can be used to investigate the role of aromatization in behavioral masculinization and defeminization, newborn male and female hamsters were administered 0.5 or 5.0 μg of the antiestrogens nafoxidine or tamoxifen on postnatal Days 1 and 2. Other females received 1.0 μg of the synthetic estrogen RU-2858 (RU) alone or in combination with 0.5 or 5.0 μg of nafoxidine or tamoxifen. All animals were tested for the display of masculine and feminine sexual behaviors in adulthood. Nafoxidine, tamoxifen, and RU all reduced lordosis behavior in adult females, indicating that the antiestrogens probably have some estrogenic properties. Nafoxidine had no effect on male mating behavior in female hamsters when given alone; when given to male hamsters or female hamsters receiving a partially masculinizing dose of RU, this compound effectively reduced the frequencies of masculine sexual behaviors (mounts and intromissions) displayed by the treated animals. However, nafoxidine-treated males had the same mating efficiency (ME = intromissions/ mounts) as control males. Tamoxifen, in contrast, facilitated the display of mounting behavior in females when given alone or in combination with RU. Male hamsters receiving 5.0 μg of tamoxifen had high mount frequencies and slightly reduced intromission frequencies, but their ME scores were only half of control levels. Thus nafoxidine itself simultaneously promoted defeminization and antagonized masculinization while tamoxifen appeared to facilitate both processes. The data support the hypothesis that estrogens derived via aromatization from androgens play an important role in both masculinization and defeminization, at least in hamsters. The differential effects of tamoxifen and nafoxidine suggest that these and other antiestrogens might serve as useful tools for dissociating and independently examining these two components of the sexual differentiation process.     

The influence of portacaval anastomosis on gonadal and anterior pituitary hormones in a rat model standardized for gender, food intake, and time after surgery

Portacaval anastomosis causes delayed growth, decreased testes and liver weights, and elevated estradiol serum levels in male rats compared with sham-operated controls. Female rats treated with portacaval anastomosis grow at a normal rate despite changes in liver weight and estradiol levels similar to those observed in the male rats. This study examined the pituitary gonadal axis in both genders in this animal model. The rats receiving portacaval anastomosis were compared with both pair-fed and sham-operated control groups. Portacaval anastomosis decreased serum testosterone and increased estradiol in the male animals, while both testosterone and estradiol were increased in the females compared with gender-matched pair-fed and sham controls. Because pair feeding lowers male testosterone to a lesser extent, impaired nutrition may partially account for the decrease in the males treated with portacaval anastomosis. The ratio of estradiol to testosterone increased following anastomosis in male rats, but it was decreased in similarly treated females. Portacaval and anastomosis decreased luteinizing hormone without changing follicle-stimulating hormone in both male and female rats compared with sham-operated controls. Growth hormone was significantly decreased in male portacaval-treated rats compared with sham- and pair-fed animals. Increased insulin levels were found in both male and female pair-fed and portacaval anastomosis-treated animals. These data suggest that following portacaval anastomosis in rats, growth, serum testosterone, estradiol to testosterone ratios, and growth hormone are altered in a gender-specific manner with gender-independent changes in insulin and luteinizing hormone levels. These gender-specific effects may protect the portacaval anastomosis-treated female rat from growth retardation.     

Sex differences in choline-deficient diet-induced steatohepatitis in mice

Alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) are common liver diseases in the United States. ASH and NASH occur more frequently in women than in men, and liver injury is also more severe in women. The role of estrogens in ASH has been well established, but their role in NASH has received relatively little study. The purpose of this study was to evaluate the effect of estrogens in methionine-choline deficient diet (MCDD)-induced steatohepatitis in mice. The degree of steatohepatitis was evaluated in males and in intact and ovariectomized females that were fed MCDD for 4 weeks, and in females that were fed MCDD containing tamoxifen. Hematoxylin and eosin-stained sections of livers showed marked steatohepatitis in all experimental groups. Compared to the control group, markers of hepatocyte injury such as aspartate transaminase (AST), alanine transaminase (ALT), and liver triglyceride levels increased significantly in males and in intact and ovariectomized female mice that were fed MCDD. Also, it was interesting that levels of AST and ALT increased much more in the MCDD + tamoxifen group than in the MCDD group. In female mice fed MCDD, hepatocyte proliferative and apoptotic indices increased slightly compared to mice that were fed a normal diet. Based on these results, it can be concluded that MCDD-induced steatohepatitis is comparable in male and female mice, and that ovariectomy or antiestrogen treatment had no protective effect in MCDD-induced steatohepatitis.     

基于氧化应激研究苦豆子不同提取物的肝毒性机制

基于亚急性毒性实验对苦豆子不同提取物肝毒性机制进行研究,为苦豆子临床安全使用提供理论依据。分别采用75%乙醇回流法(ER)、水煎煮法(WD)、75%乙醇超声法(EU)和水超声法(WU)制备苦豆子提取物,通过不同提取物的亚急性毒性实验测定大鼠肝组织中谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)、谷胱甘肽酶(GSH)、丙二醛(MDA)水平以评价其肝毒性;应用免疫组织化学和蛋白免疫印迹方法测定氧化应激相关蛋白红系衍生的核因子2相关因子(Nrf2)、血红素氧合酶1(HO-1)、超氧化物歧化酶1(SOD1)、超氧化物歧化酶2(SOD2)表达,进一步探讨其肝毒性机制。结果显示,与空白组相比,AST在雄性大鼠各给药组血清中显著性升高,ALT在雌雄大鼠血清中均呈升高趋势,尤其在雄性WD、ER组、雌性WD、WU、EU组中有显著性差异。与空白组比较,雄性给药大鼠肝脏SOD和GSH在各组中均显著性降低,GSH在雌性大鼠肝组织中呈升高趋势,其中WD组有显著性差异,MDA在雌、雄给药大鼠肝脏中均显著升高。给药后,对Nrf2/HO-1氧化应激通路中相关蛋白检测后发现,Nrf2蛋白相较空白组在肝组织中表达均呈降低趋势,其中雄性WD、WU、EU组和雌性WD、EU、ER组最为显著,HO-1在雌雄各组肝组织表达中均发生显著性降低。SOD1在雌性各组中均有显著性降低,而在雄性中WD和ER组有显著性降低。本研究发现苦豆子不同提取物对大鼠肝脏都有一定的毒性,其毒性机制主要是通过调控Nrf2/HO-1通路中相关蛋白造成机体氧化应激而发生。     

The estrogen antagonist tamoxifen inhibits carrageenan induced inflammation in LEW/N female rats

Carrageenan induces a measurable inflammatory response in susceptible animals, and mature females are more responsive to carrageenan, than males. In the present study, we tested whether the estrogen antagonist tamoxifen influences carrageenan-induced inflammatory responses. Female LEW/N rats were treated with tamoxifen and compared to a control group of animals injected with vehicle. Tamoxifen significantly reduced estrous phase of estrous cycle during treatment, consistent with its functional anti-estrogen effects. Moreover, tamoxifen significantly decreased exudate volume but did not significantly influence relative white blood cell counts in the exudate. Interestingly, tamoxifen induced differential dose-dependent alterations in peripheral blood lymphocyte subpopulations. Low dose of tamoxifen increased CD25 cells. The high tamoxifen dose significantly increased CD8 blood lymphocyte counts. Our data indicate that tamoxifen treatment decreases carrageenan-induced inflammatory response in female LEW/N rats and suggest therefore that this inflammatory response is, at least in part, estrogen related. Moreover, our results suggest a possible role for tamoxifen in treatment of inflammatory disorders.     

Protective effects of zinc in chlorpyrifos induced hepatotoxicity

The toxicological literature is replete with studies attempting to explain the mechanism of action of organophosphorus (OP) insecticides to their anticholinesterase activities, but not much is known about the metabolism and detoxification of these compounds. The goal of this study was to ascertain the toxic effects of chlorpyrifos, one of the most widely used OPs, on the liver of male rats and also to evaluate the protective potential of zinc in mediating its toxic effects. It was observed that chlorpyrifos (13.5 mg/kg body weight) treatment resulted in significant inhibition (p < 0.001) of serum and hepatic acetylcholinesterase (AChE) activities after 8 wk. However, zinc-treated (227 mg/L drinking water) animals resulted in significant normalization of the inhibited AChE activities. Similarly, a significant increase in the levels of various serum and liver marker enzymes (viz. alkaline phosphatase, aspartate aminotransferase [AST], and alanine aminotransferase [ALT]) was observed following treatment with chlorpyrifos. However, coadministration of zinc to these animals restored these enzymes to within normal limits, even though some increase in the activity of serum ALT and hepatic alkaline phosphatase still persisted at the end of the study. Chlorpyrifos treatment diminished serum and hepatic zinc levels significantly (p < 0.01 to p < 0.001) compared to normal control animals. Serum iron concentrations also plummeted significantly following chlorpyrifos treatment. On the contrary, serum copper levels were significantly increased (p < 0.01) in chlorpyrifos-treated animals, but they were normalized following zinc supplementation to the rats in this group. Interestingly, chlorpyrifos treatment resulted in elevated hepatic levels of copper, iron, and selenium, but zinc treatment could only partially restore the raised elemental concentrations. These data clearly demonstrate the potential role of zinc in mediating the toxic effects of chlorpyrifos, presumably because of their antioxidant properties and also their possible interaction with other trace elements in maintaining the cellular harmony.     

Hepatoprotective Effect of Manganese Chloride Against CCl4-Induced Liver Injury in Rats

The aim of the present study is to evaluate the protective effect of manganese chloride against carbon tetrachloride (CCl₄)-induced liver injury in rats. Manganese chloride (0.001, 0.01, 0.05 and 0.1 g/kg bw) was administered intragastrically for 28 consecutive days to male CCl₄-treated rats. The hepatoprotective activity was assessed using various biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT) and superoxide dismutase (SOD). Histopathological changes in the liver of different groups were also studied. Administration of CCl₄ increased the serum ALT, AST, ALP and GGT but decreased SOD levels in rats. Treatment with manganese chloride significantly attenuated these changes to nearly normal levels. The animals treated with manganese chloride have shown decreased necrotic zones and hepatocellular degeneration when compared to the liver exposed to CCl₄ intoxication alone. Thus, the histopathalogical studies also supported the protective effect of manganese chloride. Therefore, the results of this study suggest that manganese chloride exerts hepatoprotection via promoting antioxidative properties against CCl₄-induced oxidative liver damage.     

Biochemical response to colloidal bismuth subcitrate

In the present study, an investigation was undertaken to assess the efficacy on serum enzymes of colloidal bismuth subcitrate (CBS). CBS was administered with injections to male rats in 100-, 200-, 400-, 500-, and 1000-μg/L doses of bismuth. Rats were anesthetized at different intervals (24, 48, and 72 h) after CBS injections. The levels of serum enzymes were determined. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), and creatine kinase (CK) levels significantly increased after all CBS treatments without dependence on time. All doses of bismuth significantly affected the lactate dehydrogenase (LDH) in serum after 72 h. The lowest doses were the most toxic on ALT and LDH. These data suggest that treatment with CBS can provide evidence for a possible marker of liver toxicity although there is no evidence of liver accumulation of bismuth in the present study.     

Paradoxical hypermasculinization of the zebra finch song system by an antiestrogen

Exogenous estrogens, when administered to hatchling female zebra finches, masculinize the morphology and function of their neural vocal control system. The first of two experiments evaluated whether tamoxifen citrate is an antiestrogen in zebra finches, and the second determined whether it would block the masculinization hypothesized to be caused in hatchling males by the males' endogenous estradiol. In the first experiment adult female zebra finches were ovariectomized and injected for 10 days with estradiol benzoate (EB), tamoxifen, EB and tamoxifen combined, or vehicle (control). The dependent variable was oviduct weight. The EB-stimulated growth of the oviduct was blocked by tamoxifen, which had no effects when administered alone. Thus, tamoxifen acts as an antiestrogen in the zebra finch oviduct. In Experiment 2, male and female zebra finches were treated with tamoxifen or vehicle for the first 20 days after hatching. The males were castrated at 20 days. At 60 days we compared the song control regions of experimental and control males and females. In both sexes tamoxifen increased the somatic areas of neurons in RA (robust nucleus of the archistriatum), HVc (caudal nucleus of the ventral hyperstriatum), and MAN (magnocellular nucleus of the anterior neostriatum). Tamoxifen also increased the volumes of HVc, RA, MAN, and Area X in males. Thus, tamoxifen failed to block masculinization of males, but masculinized females and hypermasculinized males. Tamoxifen's hypermasculinization of the male and masculinization of the female song system is paradoxical given that (1) estradiol does not have similar effects on the male song system, and (2) tamoxifen antagonizes the effects of EB in the oviduct.     

Ameliorative effect of Partysmart in rat model of alcoholic liver disease

Present study was designed to investigate the effect of polyherbal formulation PartySmart in experimental model of alcoholic liver disease in male Wistar strain rats. Alcohol plus fish oil were administered to animals for 8 weeks to induce liver injury. PartySmart was administered at doses of 250 and 500 mg/kg body weight. After 8 weeks, parameters such as liver weight, liver function serum markers alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) and lipid peroxidation were studied. Livers from all the groups were subjected for histological evaluation. Treatment with PartySmart at the dose of 500 mg/kg body weight showed significant reduction in the levels of serum ALT, AST and ALP with a decrease in liver weight as compared to ethanol-fed rats. A significant decrease was also observed in malondialdehyde levels following treatment with PartySmart at 500 mg/kg body weight. Histological profile of liver tissue in PartySmart-treated animals showed lesser vacuolar degeneration and intactness of hepatic architecture along with improved glycogen deposition as demonstrated by PAS staining. PartySmart ameliorated alcohol-induced liver injury by preventing cell membrane disturbances, reduction of oxidative stress by free radical scavenging and antioxidant activity and normalization of altered intracellular redox status. Thus, PartySmart can be beneficial in the treatment of alcohol-induced liver damage.     

Pharmacokinetics of imipramine are affected by age and sex in rats

Chronic treatment with the antidepressant imipramine (IMI) leads to accumulation of imipramine's major metabolite desmethylimipramine (DMI) in the brain. Juvenile, young and middle-aged female rats, as well as juvenile and young male rats were treated chronically with imipramine (14 days) and analyzed 24 hours later for levels of IMI and DMI in the hypothalamus-preoptic area (HPA) and serum. Older animals of both sexes showed higher levels of DMI than juvenile animals, in both the HPA and serum. Females also had higher DMI levels than males at comparable ages. Analysis of IMI and DMI levels at intervals after a single imipramine injection suggested that the initial metabolism of imipramine is slower in older animals and in females (compared to males). The results indicate that age and gender alter the initial metabolism of imipramine, leading to enhanced accumulation of metabolites during chronic treatment in older animals and in female rats, compared to younger rats and males, respectively.     

Changes in serum immunoreactive inhibin and follicle-stimulating hormone during gonadal development in male and female rats.

We have measured serum and ovarian immunoreactive inhibin alpha (irI alpha) and serum FSH in fetal and neonatal rats from 20 days of gestation until 40 days of age. For animals aged 10 days or older, serum measurements were made on intact and gonadectomized animals. Serum irI alpha was detectable in intact male and female rats at all ages studied. In females, irI alpha levels were low until Day 5 and then increased steadily to peak at Day 25. Thereafter they declined until Day 35 to reach levels typical of adult females. There was a significant decrease in irI alpha levels 24 h after ovariectomy at all ages. Serum FSH levels in females were low until Day 7, then increased rapidly to plateau from Days 10-15. The levels then declined until Day 25 and were generally unchanged after that time. There was a significant increase in FSH 24 h after ovariectomy in rats aged 20 days and older, and in younger rats by 48 h after ovariectomy. In male rats, serum irI alpha levels were significantly higher than females until Day 7. The levels increased at Day 7 and then remained relatively constant until Day 20, after which they declined to reach typical adult male levels. Serum irI alpha levels were significantly lower in males than females from Days 25-40. There was a significant decrease in serum irI alpha 24 h after castration at all ages studied. Serum FSH levels in males were low until Day 20, increased at Day 25, and thereafter remained relatively unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hematological and plasma biochemical values for captive tufted capuchin monkeys (Cebus apella)

Hematological and blood biochemical parameters are of great importance in medical and veterinary practice. Unfortunately, normal reference range intervals for hematological and serum biochemical values in the tufted capuchin monkey (Cebus apella) have seldom been reported. The study reported here is based on data from blood samples collected from 44 monkeys over an 8-year period. Male and female data are displayed separately within two age categories: juveniles and adults, and effects for sex and age are examined. Significant differences between males and females are found for erythrocytes, hemoglobin, hematocrit, and α(1) globulin. Significant differences between juveniles and adults are found for neutrophils, calcium, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase, inorganic phosphorus, glucose, total protein, serum iron, and some serum protein parameters and albumin/globulin ratio. These values are compared with values we previously reported, and their importance in care and well-being of captive tufted capuchin monkeys is discussed.     

Causes and prevention of tamoxifen-induced accumulation of triacylglycerol in rat liver

Tamoxifen can induce hepatic steatosis in women. In this study, we wanted to elucidate the mechanism behind the tamoxifen-induced accumulation of triacylglycerol in liver in female rats, and we hoped to prevent this development by combination treatment with the modified fatty acid tetradecylthioacetic acid (TTA). The increased hepatic triacylglycerol level after tamoxifen treatment was accompanied by decreased acetyl-coenzyme A carboxylase (ACC) and FAS activities, increased glycerol-3-phosphate acyltransferase (GPAT) activity, and a tendency to increased diacylglycerol acyltransferase (DGAT) activity. The activities and mRNA levels of enzymes involved in beta-oxidation, ketogenesis, and uptake of lipids from liver were unaffected by tamoxifen, whereas the uptake of lipoproteins was unchanged and the uptake of fatty acids was decreased. Combination treatment with tamoxifen and TTA (Tam+TTA) normalized the hepatic triacylglycerol level and increased the activities of ACC, FAS, GPAT, and DGAT compared with tamoxifen-treated rats. The activities and mRNA levels of enzymes involved in beta-oxidation, ketogenesis, and uptake of lipids were increased after Tam+TTA treatment. In conclusion, tamoxifen increased the hepatic triacylglycerol level, probably as a result of increased triacylglycerol biosynthesis combined with unchanged beta-oxidation. The tamoxifen-induced accumulation of triacylglycerol was prevented by cotreatment with TTA, through mechanisms of increased mitochondrial and peroxisomal beta-oxidation.     

Sex-differentiated enzyme levels and oestrogen uptake in adult rats treated neonatally with tamoxifen or CI-628

Serum cholinesterase, hepatic histidase and monoamine oxidase activity levels are higher in adult female rats than in adult male rats. Exposure of neonatal rats to antioestrogen (tamoxifen or CI-628) resulted in increased serum cholinesterase in adult females only and no effect on hepatic histidase and monoamine oxidase in both sexes. Neonatal tamoxifen or CI-628 treatment resulted in reduced body weights in adult male rats and reduced uterine wet weights in adult female rats. Circulating oestrogen levels measured in adult female rats treated neonatally with tamoxifen were not significantly different from controls. Specific oestrogen uptake in the brain of adult male and female rats was found to be higher in the pituitary than in the preoptic-anterior hypothalamic area and the median eminence-basal hypothalamus than in the cerebral cortex. There was higher uptake of [3H]oestradiol-17 beta in male pituitaries than in female pituitaries. No other sex-difference was observed. Neonatal tamoxifen treatment did not alter the capacity of these brain tissues to take up oestrogen. It is suggested that neonatal antioestrogen exposure has altered the endocrine expression of serum cholinesterase in adult female rats by interfering with normal imprinting mechanisms.