Therapeutic potential of caffeic acid against alterations induced by combined exposure to Aluminum and Beryllium

The current study aimed to determine the pathological effects of chronic poisoning with sodium fluoride on some reproductive organs like ovary, and testis of adult’s male and female albino rats. Thirty-six male and female adult’s albino rats were divided into six groups. The first and second group of male and female rats are control groups was given tap drinking water, the third and fourth groups of male and female rats was given 150 ppm of NaF, the fifth and sixth group of male and female rats was given 300 ppm of NaF respectively for 90 days. The weights of male and female genital were recorded. Histological exam of control groups of female rats showed the typical histological structure of the ovary, while the NaF treated groups showed a decrease in growing follicles, in addition to thickening in tunica albuginea and deposition of eosinophilic material. In male control groups, the sections showed the typical histological structures of the testis, while the treated groups showed multinucleated spermatids in addition to the deposition of amorphous eosinophilic material in the interstitial tissue, coagulative necrosis, in addition to apoptotic and sloughed spermatogonia in the lumen of seminiferous tubule. These results indicate that sodium fluoride with 300 ppm has toxic effects on organ body weights and on the histology of the gonads of adult’s male and female albino rats.

Objective: To evaluate the postnatal toxicity of copper oxychloride (COC) in lactating female albino rats. Design: Randomized controlled experimental study. Animals: Eighteen pregnant female albino rats weight 150±10 g and 6-7 week old. Procedures: Eighteen pregnant female albino rats were divided into 3 groups treated orally with copper oxychloride 0, 73.5, 147 mg/kg (equivalent 1/20 and 1/10 of LD50) daily from first day of parturition for 21 days. Female rats and its offspring were euthanized at 21 days of treatment. The postnatal toxic effect in the neonates and dams were estimated through biochemical biomarkers as metabolic and oxidative stress biomarkers, histopathological and hematological evaluation. Results: There was a significant increase in liver enzymes activities as ALT and GGT and oxidative stress biomarker as MDA (P < 0.05) in both suckling pups and lactating dams beside decrease the level of metabolic biomarkers as glucose, total protein and cholesterol (P < 0.05). Additionally, antioxidant enzymes as SOD and CTA (P < 0.05) were reduced significantly in the treated groups in a dose dependent manner in comparison to control group. Moreover the histopathological revealed that Dams treated with COC at both doses shown degenerative changes and intralobular histiocytic infiltration with intralobular fibroblastic proliferation in the hepatic tissue. Neuronal necrosis, neuronophagia and astrocytosis in the brain tissue with degenerative changes of purkinje cells in cerebellum. Fibrous tissue proliferation of renal glomeruli with degenerative changes in renal tubular epithelium and marked lymphoid depletion in the splenic tissue in dose dependent manner. While Suckling pups of treated dams with different doses of COC shown focal histiocytic and lymphocytic infiltration besides congestion of portal vein and margination of leukocytes, focal edema in the neuropils with focal hemorrhagic areas in the brain tissue, degeneration in the renal glomeruli and severe lymphoid depletion with congestion of the splenic sinusoids in dose dependent manner. Conclusion and clinical relevance: The potential postnatal toxic effect of copper oxychloride in neonates and lactating female albino rats through transmammary transmission in milk clarified from biochemical and histopathological evaluation of dams and its pups.

Background: Piperine is a constituent of black pepper. When administered to female adult albino rats, it results in increased levels of LH and FSH, and thus causing diminished ability to procreate.
 Aim: Is determining the deleterious piperine influences on LH and FSH levels of adult female albino rats.
 Study design: It is Experimental
 Location and experiment span: Deptt. of Anatomy, FPGMI, Lahore extending from 01-08-13 to 31-01-14
 Methodology: By random selection from 30 rats, three equal groups were made, each with 10 animals. Control status was assigned to group A which was not given any medicine, but only N/S administered with the dosage 10ml/kg body wt./day by using NG tube for a span of 30 days. Group B was given piperine at dosage of 5mg/kg/day for a period of thirty days. The C group was administered drug at the dosage of 10mg per kg per day for the same period of time as A and B via the same route. At completion of thirty days of the study, the animals of the 3 groups were given euthanasia. Dissection was performed, their ovaries were removed, and after that fixed in 10% formalin. Then, 4-5 micrometer sections preparation was done by using the microtome and then H&E staining was carried out. 
 Results: FSH and LH levels in serum of group B rats was shown to have increased in comparison to control group A. The FSH and LH levels in rats of C group was greater than that in rats of B group. When the two groups were compared, this difference was determined to be extremely of significance having a p-value less than 0.001. 
 
 Conclusion: Giving Piperine to female adult albino rats was shown to cause significant increase in levels of FSH and LH which is likely to produce negative feedback on hypothalamic-pituitary-gonadal axis and in this way hamper female fertility during their productive years probably by causing PCOS.
 Key words: Piperine, Albino rat, ovaries, LH, FSH, fertility, hypothalamic-pituitary-gonadal axis, PCOS 

Silymarin is a mixture of flavonoids extracted from seeds of milk thistle (Silybum marianum [L] Gaertn ). Extracts of S. marianum have been used in the treatment of liver diseases for more than 2000 years. Flavonoids are a large group of polycyclic phenols of plant origin. Flavonoids displaying estrogenic effects (phytoestrogen). Phytoestrogens show an estrogenic activity owing to the structural similarity with the estrogen skeleton ,mimicking natural estrogens, it binds to estrogen receptor and modulates its activity . These effects cause complex changes inducing a shift in an overall hormonal balance of the individual. Long term intake of feeds with a higher content of phytoestrogens can induce transient or permanent infertility. Silybum marianum leaves have been traditionally used in Egypt for their antifertility effects .Also, the antifertility property of silybum marianum leaves was investigated in female albino rats. This property highlights the impotance to clarify the role of silymarin (420mg /day ) a human therapeutic dose on both female and male albino rats. Silymarin (151.2 mg/kg BW) prevented pregnancy in adult female albino rats on days 1-5 post coitum. In female rats the follicle stimulating hormone (FSH) displayed marked increase, while the luteinizing hormone (LH) and estradiol remained within normal levels. These results showed a distinct increase in number and size of ovarian growing follicles while the effect of silymarin on the uterine wall was in the form of hypertrophy of endometrial epithelium, also increase in the number of uterine glands. Ovaries taken from females treated with silymarin for one and two months contained a large number of growing follicles. In male rats treated with silymarin (151.2 mg/kg BW) for one month, testosterone and LH were increased significantly, meanwhile estradiol not changed. Testes of rats treated with silymarin for one month showed well developed spermatogenesis with lot of sperms. The epididymis of the same group contained a heavy number of sperms. While rats treated with silymarin for two months displayed significant decrease in serum testosterone levels, while LH and estradiol not changed. These rats displayed some tubules contained well developed spermatogenic layer and normal leyding cells, others appeared moderated by affected. The epididymis contained less number of sperms. These results indicated that silymarin (151.2mg /kgBW) a dose equivalent to human therapeutic dose (420mg/ day) prevented pregnancy in female rats and caused some histological changes in the ovary and uterus, while it has biological benefits for male rats during short treatment.

Silymarin is a mixture of flavonoids extracted from seeds of milk thistle (Silybum marianum [L] Gaertn ). Extracts of S. marianum have been used in the treatment of liver diseases for more than 2000 years. Flavonoids are a large group of polycyclic phenols of plant origin. Flavonoids displaying estrogenic effects (phytoestrogen). Phytoestrogens show an estrogenic activity owing to the structural similarity with the estrogen skeleton ,mimicking natural estrogens, it binds to estrogen receptor and modulates its activity . These effects cause complex changes inducing a shift in an overall hormonal balance of the individual. Long term intake of feeds with a higher content of phytoestrogens can induce transient or permanent infertility. Silybum marianum leaves have been traditionally used in Egypt for their antifertility effects .Also, the antifertility property of silybum marianum leaves was investigated in female albino rats. This property highlights the impotance to clarify the role of silymarin (420mg /day ) a human therapeutic dose on both female and male albino rats. Silymarin (151.2 mg/kg BW) prevented pregnancy in adult female albino rats on days 1-5 post coitum. In female rats the follicle stimulating hormone (FSH) displayed marked increase, while the luteinizing hormone (LH) and estradiol remained within normal levels. These results showed a distinct increase in number and size of ovarian growing follicles while the effect of silymarin on the uterine wall was in the form of hypertrophy of endometrial epithelium, also increase in the number of uterine glands. Ovaries taken from females treated with silymarin for one and two months contained a large number of growing follicles. In male rats treated with silymarin (151.2 mg/kg BW) for one month, testosterone and LH were increased significantly, meanwhile estradiol not changed. Testes of rats treated with silymarin for one month showed well developed spermatogenesis with lot of sperms. The epididymis of the same group contained a heavy number of sperms. While rats treated with silymarin for two months displayed significant decrease in serum testosterone levels, while LH and estradiol not changed. These rats displayed some tubules contained well developed spermatogenic layer and normal leyding cells, others appeared moderated by affected. The epididymis contained less number of sperms. These results indicated that silymarin (151.2mg /kgBW) a dose equivalent to human therapeutic dose (420mg/ day) prevented pregnancy in female rats and caused some histological changes in the ovary and uterus, while it has biological benefits for male rats during short treatment.

Zinc and selenium mitigated heavy metals mixture (Pb, Al, Hg and Mn) mediated hepatic-nephropathy via modulation of oxido-inflammatory status and NF‑kB signaling in female albino rats

Increased serum lipid levels are associated with the increased risk of many metabolic disorders including cardio vascular disease (CVD), obesity and diabetes mellitus.The objective of the current study was to determine whether feeding salmon diet with omega-3 polyunsaturated fatty acids (n-3 PUFAs) will alter serum lipid profile in male and female rats after three months of feeding.Although many studies have focused on the role of salmon fish on human health the results remain controversial.Consequently, the question of whether or not salmon fish are beneficial or harmful to lipid profile remains unresolved.Male and female Wistar albino rats were used in the present study.Each sex was randomly divided into two groups (n= 20 per group).Control group: fed on the rodent diet AIN-93G which was recommended by the American Institute of Nutrition for growth, pregnancy and lactation.Salmon diet treated group: each rat was fed individually on cooked salmon fish diet 0.34 ‫ـــ‬ 0.69 gm/ rat which is equivalent to 200 gm / 70 kg human body weight then were all given AIN-93G diet ad-libitum for three months.At the end of the experimental period the results showed that compared to the control group salmon diet significantly decreased serum levels of total cholesterol (TC) and triglycerides (TG) and significantly increased serum high-density lipoprotein (HDL-C) level however no effects were detected on serum low-density lipoprotein (LDL-C), glucose, insulin and body weight in male rats.Also in female rats salmon diet significantly decreased serum levels of TC and TG but no effect on HDL-C, LDL-C, glucose, insulin and body weight was observed.These results suggest that salmon meal play a protective role from cardio vascular disease (CVD) by decreasing lipid profile.

Metal contamination poses a significant health concern driven by industrialization, landscape modifications, and rapid urbanization. Aluminum and beryllium exposure has been associated with multiple organ dysfunction, including liver, kidney and brain. In present study investigates therapeutic effects of caffeic acid in mitigating liver, kidney and brain damage induced by combined exposure to aluminum and beryllium in female rats. Rats were assigned into five groups. Group 1 served as control. Groups 2-5 were exposed to combination of aluminum nitrate (6.5 mg/kg, i.p.) and beryllium nitrate (1 mg/kg, i.p.) daily for 4 weeks. Groups 3, 4, and 5 received oral doses of caffeic acid (10, 20, and 30 mg/kg, respectively) for 2 weeks after 2 weeks of exposure to toxicants. After 24 h of the last treatment, animals were euthanised, followed by hematology, liver kidney and brain function tests, oxidative stress and antioxidant status in studied organs. Combined exposure to metals significantly altered hematology, liver, kidney and brain function markers. Enzymatic antioxidant defenses, including reduced glutathione, catalase, superoxide dismutase, glutathione peroxidase, glutathione reductase, glutathione Sulfur transferase, and glucose-6-phosphate dehydrogenase were compromised, whereas lipid peroxidation and cholesterol levels were significantly increased. Histological observations revealed organ injury due to toxic effects of combined exposure to aluminum and beryllium. Caffeic acid treatment exhibited a dose-dependent recovery in these parameters and restored them towards control. These findings suggested that caffeic acid may perform therapeutic role by exerting direct and indirect antioxidant effects against combined exposure to aluminum and beryllium induced injury in multiple organs.

Aluminum (Al) and Beryllium (Be) are light metals, widely used across various sectors. The present study was conducted to investigate toxic effects of Al and Be alone and their combination on hematology and electrolytes in female albino rats. Rats were administered with aluminum nitrate 6.5 mg/kg, i.p. and beryllium nitrate 1 mg/kg, i.p. for continuous 28 days followed by rest for 07 days. On 36th day, animals were euthanized; blood was collected through retro-orbital venous sinus for hematology and electrolytes. The findings revealed alterations in RBCs, WBCs, Hb, PLT, MCV, HCT, PLCR, MCH, MCHC, PCT and MPV. Significant variations in Na+, K+, Cl- and iCa2+ ions were noted in electrolytes in serum. Thus, it can be concluded that individual and combined exposure to Al and Be exert toxic effects by remarkable alterations in hematology and electrolytes; however, combined exposure imposes more pronounced toxic effects.

Organophosphates (OPs) have been shown to induce oxidative stress (OS) by elevating levels of reactive oxygen species and genotoxic effects by the irreversible damage to the various organs. Present study reports the toxic effects of profenofos on female albino rats at two sub-chronic doses of 1/10th and 1/50th of LD50, administered for six weeks each. Activity levels of antioxidative enzymes viz: catalase (CAT), superoxide dismutase (SOD), glutathione-S-transferase (GST), glutathione reductase (GR), glutathione peroxidase (GPx) and lipid peroxidation (LPO) were differentially altered in liver, kidneys and ovaries of profenofos treated rats as compared to control. The total antioxidant activity (AOA) was also significantly decreased in the plasma of profenofos treated rats. Increased frequencies of micronucleated polychromatic erythrocytes in bone marrow cells of treated rats also indicated the genotoxic effect of profenofos. The results infer that profenofos induces oxidative stress and genotoxicity in female albino rats in a dose dependent manner.

A substantial number of the world population especially that of the developing countries rely on herbal products to control their fertility since ancient times. Rumex steudelii Hochst is one of the traditionally used antifertility plants in Ethiopia. Previous studies showed that the methanolic root extract of the plant had reversible antifertility effect in experimental animals. However, no study had hitherto been done on the antifertility activity of the methanolic root extract of Rumex steudelii on the ovary and uterus of female albino rats. To investigate the quantitative aspects of follicular development in the ovaries and uterine histology in cyclic female albino rats to get further information on the possible mechanism of antifertility effect of the methanolic extract of R. steudelii. The effect of the extract on uterine histology and ovarian follicular growth was determined after oral administration of the methanolic root extract of Rumex steudelii at 2.2, 2.5, 3.0 g/kg/day doses consecutively for 30 days. The extract significantly decreasing the number of healthy small antral, Graffian follicles and corpora lutea with concomitant significant increase in the number of atretic follicles of the same stage in dose dependent manner. Treatment at 3.0 g/Kg dose level in addition caused a significant decrease in the number of healthy primary, small preantral and large preantral follicles with concomitant significant increase in the number of atretic primary follicles. The ovarian and uterine wet weights are reduced significantly. The extracts also caused a significant decrease in the epithelial cell height, myometrial and stromal thickness in a dose dependent manner. The study demonstrated that the methanolic extract could cause atrophic changes in the uterus and disruption of ovarian folliculogenesis by inhibiting further development of the recruited ovarian follicles.

Background: The suprachiasmatic nucleus (SCN) is one of the nuclei in the anterior hypothalamus superior to the optic chiasma. It is well known that vasopressin and oxytocin neurons are located in the hypothalamic para-ventricular and the supraoptic nuclei. Extensive vasopressin neurons were observed in the rostral and middle regions of the suprachiasmatic nucleus.Aim of the work: Although the presence of oxytocin immunoreactive neurons within the SCN is unusual, this study was designed to clarify immunohistochemical localization of oxytocin neurons in the suprachiasmatic nucleus in the male and pregnant female adult albino rat and to investigate morphometrical differences in those neurons in relation to the gender.Material and Methods: Twenty adult rats (10male and 10 non pregnant female) were involved in this study. Rats were anaesthetized with ketamine, sacrificed and their brains were carefully dissected. The anterior portion of the hypothalmus containing the suprachiasmatic nucleus was taken. Coronal sections of the brain were prepared for histological stains (Hematoxylin and Eosin) and immunohistochemical stain (Oxytocin immunostaining). The diameters and number of oxytocin labelled neurons in the suprachiasmatic nucleus in each group were measured in a fixed field. The data will be used for morphometrical study.Results: The SCN in rat was formed mainly of 2 regions according to the change in the shape, rostral SCN (rSCN) and caudal SCN (cSCN).The rSCN appeared as a collection of neurons basal to the third ventricle and superior to the optic chiasma. It showed mixture of bipolar and multipolar cells. The cSCN was formed of mixture of large rounded and small bipolar neurons. The rostral part of the nucleus showed positive OT immune-reactive neurons throughout its structure in both male and female rats, the caudal part of the nucleus exhibited OT immune-reactive neurons in the lateral part only on both sides of the third ventricle, while its medial potion showed negative reaction for OT in both groups.Conclusion: The present findings proved immunehistochemical identification of OT neurons in the adult male and nonpregnant female rat SCN, and indicate clear sex differences in OT neurons morphometrical measurements which may be parallel to differences in the neuroendocrine and behavioral function in both sexes.

Liv-52 protection against beryllium toxicity in female albino rats

Assessment of the antidiabetic effect of cinnamon bark extract in histologic damages and some hematologic parameters in Alloxan® induced diabetic female albino rats. Thirty female albino rats weighing 150-230g were divided into five groups (n = 6): normal (G1) and diabetic groups (intraperitoneally Alloxan®-injected) including diabetic control (G2), Getformin @ 0.25 (G3), CE @ 0.10 (G4), and CE @ 0.20g/kg b.wt. (G5) for 49days. Blood glucose level and weight were measured on weekly interval for the period of seven weeks (49th day). Blood samples were collected for hematologic analysis. Tissue samples from uterus, liver and kidneys were processed by routine paraffine technique. Histologic sections of uterus were studied to measure endometrial glands area and thickness of endo- and myometrium. Liver and kidneys were evaluated for diabetes-induced degenerative changes andantidiabetic effect of cinnamon extract(CE). One-way analysis of variance followed by Tukey test were used to compare the group means for each parameter. Statistical analysis revealed significant (P < 0.05) deleterious effects of diabetes on all parameters studied, however, CE recovered hematological parameters significantly (P < 0.05) as seen in G3 and G5 groups which showed significant (P < 0.05) improvement in uterus, liver and kidneys' histology. G4 significantly (P < 0.05) reduced the blood glucose at the 4th week which was maintained in subsequent weeks while G3 and G5 had significantly (P < 0.05) lowered the blood glucose from 1st week, although highly significant (P < 0.01) effect was observed during last two weeks of the study. Anti-diabetic activity of cinnamon extract was found significant in Alloxan® induced hyperglycemic rats in dose-dependent manners. CE has potential to restore diabetes induced hematological disturbances and histological damages in uterus, liver and kidney due to the presence of cinnamic acid, anhydride tannin and methyl-hydroxy chalcone polymer. Hence, CE can be recommended for the management of glucose homeostasis to avoid diabetes-associated disturbances in female rats.

The study investigated the effect of testosterone administration on the eating and mating behaviour of female albino rats. Nine (9) female Wister (albino) rats and three (3) stimulus male albino rats were obtained from the Faculty Pharmacy, University of Uyo, Uyo. The female albino rats weighed 165 to 215 g before administration of testosterone, and 173 to 235 g during the experimental week. The age range of the rats was from 10 to 12 weeks with a mean age of 11 weeks. A within-subject design was used in the study, with a judgmental/purposive non-probability sampling technique adopted. The females were grouped in threes and labelled group 1, group 2, and group 3 while the 3 males were housed in one cage and labelled accordingly. Before the commencement of the experiment, the rats were allowed to acclimatize for a period of two weeks of which food and waters were given ad libitum. After the first nine days, two female albino rats were sampled from the cages – group 1 (rats B and C), group 2 (rats D and E), and group 3 (rats G and H) for blood samples collection to determine their testosterone levels before administration of testosterone propionate. During the experiment, the females’ rats were administered difference level of testosterone concentration. Group 1 was administered 0.5 ml testosterone concentration (low dose), group 2 received 1 ml testosterone concentration (medium dose), and group 3 received 1.5 ml testosterone concentration (high dose). Thereafter, testosterone analysis was carried out on the blood samples collected from the female rats; testosterone concentration in the rats after administration was greater than testosterone concentration before administration. The paired sample t-test and one-way MANOVA was used to analyse the data generated. Results obtained showed that when testosterone levels of the female albino rat increased following testosterone administration, their mean eating behaviour increased from 36.77 to 85.44, while their mean mating behavior also increased from 34.44 to 44.88. Thus, the H1 paired sample t-test showed a t-value of -3.091 with df of 8. The result was significant with p&lt;0.0005, so H1 was accepted. For H2, t-value was also significant at t = -2.74, p&lt;0.005, df of 8 and also accepted. H3 was also significant and accepted at [f (2, 8) = 21.57; p &lt; 0.05] and [F = (2, 8) 7.706; p &lt; 0.05] respectively. In conclusion, the female albino rats eat more after testosterone administration. They also engaged more in mating behaviour after testosterone administration. Hence, the study recommends that married women who have a sexual desire should use testosterone replacement therapy for better results. This should, however, be used moderately.