Subacute Oral Administration Research Articles

Acute and repeated doses (28 days) oral toxicity study of glycosides based standardized fenugreek seed extract in laboratory mice

The objective of the present work was to study acute and subacute (28-days repeated dose) oral toxicity effect of glycosides based standardized fenugreek seed extract (SFSE-G) in vivo. SFSE-G was prepared by resin-based chromatography and standardized to glycosides namely trigoneoside Ib (76%) and vicenin 1 (15%). The acute oral toxicity (AOT) and subacute toxicity studies were performed in Swiss albino mice (5 mice/sex/group) as per OECD 425 (up-and-down procedure) and OCED 407 guidelines respectively. Acute oral administration of 5000mg/kg of SFSE-G showed 40% mortality with no mortality in lower dosages. The subacute oral administration of SFSE-G did not show observational or toxicological effects on the body or organ weights, food consumption, ophthalmic effects, locomotor activity, hematology, blood biochemistry, urinalysis, or histopathology at dose 250mg/kg. However, SFSE-G (1000mg/kg) showed mortality and minor alterations to body weight, relative liver weights, hematology and blood chemistry parameters related to treatment but it was within normal laboratory ranges. In conclusion, SFSE-G showed median lethal dose (LD50) more than 4350mg/kg and no-observed adverse effect levels (NOAEL) of 250mg/kg for both sexes during AOT and sub-acute toxicity study, respectively.

Evaluation of Sub-acute Oral Toxicity of Lithium Carbonate Microemulsion (Nano Size) on Liver and Kidney of Mice.

The development of drug delivery systems has improved the therapeutic and toxic properties of existing drugs in therapy. Microemulsion systems are novel vehicles for drug delivery, which have been developed in recent years. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating into a wide range of drug molecules. Although these systems improved solubility and bioavailability of drugs, they may have potential toxic effects on the body organs. The purpose of this study was to examine a possible hepatotoxic and nephrotoxic effect of lithium carbonate microemulsion (LCME) in a mice model. Eighty male Swiss albino mice were randomly allocated to eight experimental groups, as follows: Group 1, as negative control group were treated orally with normal saline (0.9% NaCl); Group 2, received microemulsion base without drug as control group; Groups 3 to 5, received lithium carbonate (LC) solution in doses of 50, 100, and 200 mg/kg, respectively; Groups 6 to 8, received LCME orally in doses of 50, 100, and 200 mg/kg, respectively. All drugs were administered orally for ten consecutive days. Serum glutamate pyruvate aminotransferase (SGPT), serum glutamate oxaloacetate aminotransferase (SGOT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), and plasma creatinine (Cr), as markers of liver and kidney toxicity in treated mice, were measured. Furthermore, the changes of tissue were assessed by histopathologic examination. The findings showed that serum activity of ALP, SGOT, and SGPT and the levels of BUN and Cr in microemulsion base group was greater than normal saline group. However, this difference was not significant. Administration of LC and LCME in all doses resulted in a significant increase in the levels of BUN and serum activity of SGOT and SGPT in comparison to normal saline group (P < 0.05). Histopathological changes were observed in mice treated with LC or LCME. This study showed that subacute oral administration of different doses of LCME with severe toxicity in comparison to the same dose of LC.

Effects of SiO₂, ZrO₂, and BaSO₄ nanomaterials with or without surface functionalization upon 28-day oral exposure to rats.

The effects of seven nanomaterials (four amorphous silicon dioxides with or without surface functionalization, two surface-functionalized zirconium dioxides, and barium sulfate) upon 28-day oral exposure to male or female rats were investigated. The studies were performed as limit tests in accordance with OECD Test Guideline 407 applying 1,000 mg test substance/kg body weight/day. Additionally, the acute phase proteins haptoglobin and α2-macroglobulin as well as cardiac troponin I were determined, and metabolome analysis was performed in plasma samples. There were no test substance-related adverse effects for any of the seven nanomaterials. Moreover, metabolomics changes were below the threshold of effects. Since test substance organ burden was not analyzed, it was not possible to establish whether the lack of findings related to the absence of systemic exposure of the tested nanomaterials or if the substances are devoid of any potential for toxicity. The few published subacute oral or short-term inhalation studies investigating comparable nanomaterials (SiO2, ZrO2, and BaSO4) also do not report the occurrence of pronounced treatment-related findings. Overall, the results of the present survey provide a first indication that the tested nanomaterials neither cause local nor systemic effects upon subacute oral administration under the selected experimental conditions. Further investigations should aim at elucidating the extent of gastrointestinal absorption of surface-functionalized nanomaterials. Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-014-1337-0) contains supplementary material, which is available to authorized users.

Evaluation of Biochemical Parameters in Buffalo Calves Exposed to Subacute Fenvalerate Toxicosis

Pesticides being used for the control of agricultural pests and insects causing public health hazards, are responsible for certain ailments and/or outbreaks reported amongst animals and humans, which usually occur either from direct exposure to insecticides or indirectly from contaminated feeds or water by such chemicals. In the present investigation, oral subacute toxicity study of fenvalerate, a pyrethroid insecticide, was undertaken in male buffalo calves. Repeated oral administration of fenvalerate at 1.0 mg kg−1 day−1 for 21 consecutive days in buffalo calves did not exhibit any significant toxic signs in buffalo calves. It however produced significant elevation in plasma aspartate aminotransferase (21.5 %), gamma glutamyl transpeptidase (43.9 %), glucose (39.9 %) and creatinine (37.7 %). Subacute oral administration of fenvalerate did not produce any significant effect in the levels of alkaline phosphatase, lactate dehydrogenase, creatine kinase, total plasma proteins, albumin, cholesterol and blood urea nitrogen. Present investigation reveals that fenvalerate is a moderate-risk insecticide in buffalo calves.

Cute and Sub-Acute Toxicity Studies of Plumeria alba Linn. (Apocynaceae) Hydroalcoholic Extract in Rat

Plumeria alba Linn (Apocynaceae) is used in Togolese traditional medicine to treat diabetes mellitus and wounds. The present investigation was carried out to evaluate the toxicity of hydroalcoholic extract of Plumeria alba roots in Sprague Dawley rats. The acute toxicity test was conducted by administering orally dose of 5 g/Kg. General behavior and mortality were examined for up to 14 days. The sub-acute toxicity test was performed by daily gavage at 250, 500 and 1000 mg/Kg for 28 days. Body weight and blood glucose were measured weekly. Hematological and biochemical parameters, relative organ weight were determined at the end of the 28 days administration. In acute study, no adverse effect of the extract was observed at 5.0 g/Kg. Sub-acute oral administration of the extract at the dose up to 1000 mg/Kg did not induce death or significant changes in body weight, relative weight of vital organs, hematological parameters and was not associated with liver and kidney toxicity.

Effect of exposure to diazinon on adult rat’s brain

Diazinon (DZN), a commonly used agricultural organophosphate insecticide, is one of the major concerns for human health. This study was planned to investigate neurotoxic effects of subacute exposure to DZN in adult male Wistar rats. Animals received corn oil as control and 15 and 30 mg/kg DZN orally by gastric gavage for 4 weeks. The cerebrum malondialdehyde and glutathione (GSH) contents were assessed as biomarkers of lipid peroxidation and nonenzyme antioxidants, respectively. Moreover, activated forms of caspase 3, -9, and Bax/Bcl-2 ratios were evaluated as key apoptotic proteins. Results of this study suggested that chronic administration of DZN did not change lipid peroxidation and GSH levels significantly in comparison with control. Also, the active forms of caspase 3 and caspase 9 were not significantly altered in DZN-treated rat groups. Moreover, no significant changes were observed in Bax and Bcl-2 ratios. This study indicated that generation of reactive oxygen species was probably modulated by intracellular antioxidant system. In conclusion, subacute oral administration of DZN did not alter lipid peroxidation. Moreover, apoptosis induction was not observed in rat brain.

Effects of Gmelina arborea extract on experimentally induced diabetes

ObjectiveTo study the effects of aqueous extract of Gmelina arborea bark on normoglycemic levels and streptozotocin (STZ) induced diabetes in rats. MethodsAfter single administration of the aqueous extract, plasma glucose level was determined up to 6 h. In subacute study, the aqueous extract was administered for 28 d and plasma glucose level was determined weekly. The diabetes was induced in rats by the intraperitoneal injection of STZ at a dose of 55 mg/kg body weight. The diabetic animals were divided into four groups containing six in each: Group I diabetic control, Group II and III treated with the aqueous extract respectively at a dose of 250 and 500 mg/kg body weight once daily and Group IV treated with glibenclamide at a dose of 0.6 mg/kg body weight once daily. In acute study, the aqueous extract and glibenclamide were administered orally to rats. Plasma glucose levels were determined at 30, 60, 120, 240 and 360 min after the administration of the test samples. To study subacute effects, test samples (the aqueous extract and glibenclamide) were administered for 28 d consecutively. The effects of each test sample on plasma glucose level, body weight as well as food and water intake were also monitored weekly. The oral glucose tolerance test and biochemical indicators were estimated on day 28. ResultsThe aqueous extract did not significantly decrease the plasma glucose level in the normoglycemic rats as shown by the acute and subacute assays. However, after oral administration of the aqueous extract, the plasma glucose level was significantly (P<0.001) decreased in the diabetic rats in the acute study. The long-term administration of the aqueous extract significantly (P<0.001) reduced plasma glucose levels of the diabetic rats. Additionally, the aqueous extract also reduced loss of body weight and significantly decreased food and water intake in the diabetic animals. Nevertheless, no effects on biochemical indicators were observed at the selected doses. ConclusionsThe aqueous extract of Gmelina arborea bark had antihyperglycemic activity against STZ induced diabetes in rats, after single and subacute oral administration. Moreover, it did not show significant glucose lowering effect in normoglycemic rats.

Fipronil-Induced Biochemical Alterations During Oral Subacute Toxicity in Buffalo Calves

In the present investigation, detailed oral subacute toxicity study of fipronil, a phenylpyrazole insecticide, was undertaken in male buffalo calves. In oral subacute toxicity study, fipronil was administrated to male buffalo calves at repeated oral dose of 0.5 mg kg−1 day−1 for 21 consecutive days. Fipronil produced varying degree of mild to moderate toxic signs in buffalo calves. Fipronil produced toxic signs of salivation, lachrymal discharge, dullness, depression, decreased body weight gain, alopecia and sunken eyes. All the fipronil-exposed animals recovered within 7 days after insecticidal treatment was stopped. Repeated oral administration of fipronil at the dose rate of 0.5 mg kg−1 day−1 for 21 consecutive days produced significant elevation of whole blood cholinesterase to the extent of 45.17 %. Fipronil on repeated oral administration produced significant increase in the plasma levels of lactate dehydrogenase (7.08 %), aspartate aminotransferase (43.55 %) and acid phosphatase (11.647), but no significant effect on the plasma levels of alanine aminotransferase and alkaline phosphatase in male buffalo calves. Subacute oral administration of fipronil elevated the levels of gamma-glutamyl transferase (25.53 %), total plasma proteins (20.59 %) and blood glucose (40.75 %). However, no significant alteration in the levels of blood urea nitrogen, plasma creatinine and cholesterol was seen following daily oral administration of fipronil in the buffalo calves.

Effect of Sub-Acute Oral Exposure of Bifenthrin on Biochemical Parameters in Crossbred Goats

Bifenthrin is an insecticide, used extensively on some crops, including corn. Roughly 70 % of all US-grown hops and raspberries are treated with bifenthrin. The current study on bifenthrin was undertaken to investigate the potential alterations in biochemical parameters, induced by sub-acute oral exposure of bifenthrin, in goats. The animals were randomly divided into two groups. Group A (n = 3) received only tap water and served as control, whereas, Group B goats (n = 4) received bifenthrin by gavage (Telstar 10 EC) at the dose rate of 5 mg Kg−1 body weight for 28 consecutive days. Bifenthrin exposed group showed significant alterations in the enzyme biochemical parameters. The activities of erythrocyte cholinesterase and plasma cholinesterase reduced significantly from 7th day and 28th day of bifenthrin exposure, respectively. The activity of plasma aspartate aminotransferase and alanine aminotransferase increased significantly from the 21st day of bifenthrin exposure. The activity of acid phosphatase and alkaline phosphatase increased significantly from the 14th day of bifenthrin exposure. All these parameters returned to the non-significant levels by 7th day of post-exposure period. Non-significant alterations in blood urea nitrogen, creatinine and plasma proteins were also observed. The current study thus reveals that sub-acute oral administration of bifenthrin produces reversible liver damage.

Dose-dependent antihypertensive determination and toxicological studies of tilianin isolated from Agastache mexicana

Ethnopharmacological relevanceAgastache mexicana is used in Mexican traditional medicine for the treatment of hypertension, anxiety and related diseases. Aim of the studyCurrent work was developed to establish pharmacological/toxicological parameters of tilianin, a flavone extracted from Agastache mexicana in order to propose it for clinical trials. Materials and methodsAcute and sub-acute toxicology studies in Imprinting Control Region (ICR) mice and median effective dose (ED50) determination in conscious spontaneously hypertensive rats (SHR) were done. ResultsA median lethal dose (LD50) of 6624mg/kg (6201, 7076) in mice and significant antihypertensive effect (ED50=53.51mg/kg) in SHR were determined. Moreover, sub-acute oral administration of tilianin did not alter body weight, clinical chemistry parameters (alanine amino-transferase, aspartate amino-transferase, total cholesterol, high density lipoprotein, low density lipoprotein, triglycerides, glucose and insulin), and also did not induce any toxic or adverse effects on kidney, heart, liver, and lung functions. ConclusionsWe have shown that tilianin, isolated from Agastache mexicana, was not toxic for rodents. Also, its antihypertensive effect was dose-dependent and ED50 (53.51mg/kg) calculated was lesser than LD50 determined (6624mg/kg), which suggest a wide range of pharmacology–toxicology patterns. Results support the hypothesis that tilianin must be investigated and developed for clinical trials as antihypertensive drug.

&lt;i&gt;Catha edulis&lt;/i&gt; F. (Khat) Reverses Haloperidol But Not Morphine Induced Motor Deficits Following Acute and Subacute Administration in Mice

Khat (Catha edulis F.) is widely chewed in Africa and the Middle East. The use of the plant is associated with different central and peripheral effects. The aim of this study is to evaluate acute and subacute effects of crude khat extract in haloperidol and morphine-pretreated mice by measuring behavioural and biochemical parameters. Crude khat extract obtained using a mixture of chloroform and diethyl ether (1:3) was administered orally in doses of 100, 200 and 300 mg/kg as a single dose and repeatedly for fourteen days, and motor parameters, including catalepsy and locomotor behaviour as well as biochemical markers for oxidative stress, such as activity of superoxide dismutase (SOD) were measured. Whilst acute and subacute oral administration of khat failed to reverse morphine-induced motor deficits, it was capable of reversing the haloperidol-induced one in a manner that depended on time and dose. In both settings, khat at 200 and 300 mg/kg dose as well as amphetamine (50 mg/kg) produced a consistent improvement in motor performance. The effects observed were either comparable or better than amphetamine. By contrast, both khat (300 mg/kg) and amphetamine increased plasma SOD activity in both haloperidol and morphine pretreated animals. SOD activity increase was significantly higher in khat 300 mg/kg compared to haloperidol/morphine pretreated controls (p&lt;0.001) as well as amphetamine treated (p&lt;0.05) mice. The findings collectively indicate that haloperidol induced motor abnormalities are mediated by the dopaminergic system, while morphine may utilize other pathways in causing such deficits. Moreover, modulation of SOD although considered to be a contributing factor in reversing haloperidol-induced motor deficit, it might not be sufficient to prevent that induced by morphine.Keywords: Catha edulis, motor activity, superoxide dismutase, haloperidol, morphine

Effects of subacute oral warfarin administration on peripheral blood granulocytes in rats

Warfarin affects mainly vitamin K dependent (VKD) processes, but the effects on some non-VKD-related activities such as tumor growth inhibition and mononuclear cell-mediated immune reactions were shown as well. In this study, the effect of subchronic (30days) oral warfarin (0.35mg/l and 3.5mg/l) intake on peripheral blood granulocytes in rats was investigated. Increase in prothrombin and partial thromboplastin time at high warfarin dose reflected its basic activity. Priming effect for respiratory burst was noted at both warfarin doses, while only high warfarin dose resulted in priming for adhesion, the rise in intracellular myeloperoxidase content/release and stimulation of nitric oxide production. Differential effects of high warfarin dose were noted on granulocyte cytokines IL-6 (lack of the effect), TNF-α (decreased release and mRNA expression) and IL-12 (increase in mRNA for IL-12 subunits p35 and p40). Changes in granulocytes seems not to rely on mitogen activated kinases p38 and ERK. Warfarin intake was associated with an increase in circulating IL-6, fibrinogen and haptoglobin and with changes in the activity of erythrocyte antioxidant enzymes superoxide dismutase and catalase. The effects of oral warfarin intake on peripheral blood granulocytes demonstrated in this study might be relevant for oral anticoagulant therapy strategies in humans.

Toxicological Evaluation of &lt;i&gt;Murraya Paniculata&lt;/i&gt; (L.) Leaves Extract on Rodents

Problem statement: Present study was aimed to explore the acute and s ub-acute toxicities studies with orally administered 50% ethanolic leav es extract of Murraya paniculata . Approach: Acute toxicity (oral single dose, 50-2000 mg kg -1 ) includes any mortality and CNS and ANS toxicities in mice while, sub-acute toxicity (100, 200 and 400 mg kg -1 , orally and once daily for 28 days) includes any change in body weight, food and water intake and other biochemical, hematological and histopathological changes in tissues (liver, ki dney, spleen, stomach, heart and lung) in rats. Results: Acute oral administration of M. paniculata extract (2000 mg kg -1 , single dose) did not show any mortality and CNS and ANS toxicities. Similarly sub-acute oral administration (100, 200 and 400 mg kg -1 for 28 days) in rats did not show any change in bo dy weight, food consumption, water intake and biochemical, hematological and histopathological parameters compared to control untreated group. Conclusion: The conclusions of the present study indicate Murraya paniculata to be safe in its oral effective dose.

Prallethrin induced serum biochemical changes in Wistar rats

The present study was designed as a repeated dose 28-day oral toxicity study in rodent. All the rats were randomly divided into five groups (C1, C2, T1, T2 and T3) each containing 10 Wistar rats (5 male and 5 female). Group C1 served as control as no treatment was administered. Group C2 was administered groundnut oil (1ml/100g b.wt) and served as vehicle control. Group T1 was put on high dose 153.33mg/kg b.wt (LD50/3), while group T2 received intermediate dose of 92mg/kg b.wt (LD50/5), and group T3 was administered low dose of 46mg/kg b.wt (LD50/10) of Prallethrin suspended in 1ml/100g b.wt of groundnut oil. Blood samples were collected from all groups on the 7th, 14th, 21st and 28th day of the experiment for measurement of serum glucose, serum urea, serum triglyceride, serum cholesterol, serum aspartate aminotransferase (AST), serum alanine aminotransferase (ALT) and serum alkaline phosphatase (ALP). According to data obtained on the 7th day of the study, no statistically significant change in any of the treatment groups was observed as compared to the control group. On the 14th day of the study, in comparison to the control group, triglyceride level and ALP activity were found to be significantly increased in the group T1 female and group T1 male rats respectively. On the 21st day of the study, compared to the controls, significant increase in cholesterol and ALP levels were present in both T1 and T2 females and in addition to this total protein and triglycerides levels were also significantly increased in group T1 female rats. In group T1 male total protein, triglycerides, ALT and ALP activity was found to be increased significantly as compared to healthy control group. On the 28th day, all the recorded biochemical parameters were found to be significantly increased, except BUN and AST in group T1 female rats. In group T2 female rats, significantly increased cholesterol, ALT and ALP levels were observed. In group T3 female rats, none of the parameters were found to be significantly affected. Among male rats, only total protein level was found to be increased in groups T2 and T3. Whereas, total protein, triglyceride, ALT and ALP were significantly elevated in group T1 male rats at the end of the study. In conclusion, the results of this study demonstrate that subacute oral administration of Prallethrin; at dose levels of 1/3 LD50 and 1/5 LD50 for 28days induces moderate toxic effects on different biochemical parameters.

Effects of subacute oral administration of captopril (SQ 14,255) on the renin-angiotensin system in spontaneously hypertensive rats.

Effects of subacute oral administration of captopril (SQ 14,255) on the renin-angiotensin system in spontaneously hypertensive rats.

Some Biochemical Effects of Sub-Acute Oral Administration of L-Arginine on Monosodium Glutamate-Fed Wistar Albino Rats 2: Serum Alkaline Phosphatase, Total Acid Phosphatase and Aspartate Aminotransferase Activities

Some Biochemical Effects of Sub-Acute Oral Administration of L-Arginine on Monosodium Glutamate-Fed Wistar Albino Rats 2: Serum Alkaline Phosphatase, Total Acid Phosphatase and Aspartate Aminotransferase Activities

Toxicity of subacute oral administration of cypermethrin in rats with special reference to histopathological changes

Pyrethrins are obtained from the flowers of Chrysanthemum cinerarifolium. These are strong insecticides with low mammalian toxicity. The toxic effects of pyrethroid cypermethrin were studied using various biochemical parameters along with histopathological changes in a 30-day study in Wistar rats. The rats were divided into two groups. Rats of the test group were given sublethal doses of cypermethrin (14.5 mg/kg) by gavage once daily for 30 days and the control rats were given an equal volume of the vehicle. The animals were sacrificed on day 0, 10, 20 and 30 of the study. The results showed that cypermethrin caused a significant increase in the levels of serum aspartate transaminase, alanine transaminase, lactate dehydrogenase and plasma creatinine. It significantly lowered the levels of total proteins. The histopathological studies on various organs like liver, lungs, kidneys and heart were carried out. The changes in various biochemical parameters correlated well with the histopathological changes in various organs. In conclusion, the results of this study demonstrate that subacute oral administration of cypermethrin, even in low doses such as 1/10 LD50 for 30 days induces toxic effects on different vital organs. Key words: Chrysanthemum cinerariifolium, pyrethrins, subacute toxicity

Subacute oral administration of low dose 17 β -estradiol or 17 α -ethinyl estradiol does not markedly alter the immune system of young adult and aged C57BL/6 mice

Due to growing awareness that estrogens and their metabolites are leaked into the environment at low concentrations through wastewater and agricultural run-off, it is increasingly important to examine the potential adverse health effects of environmental exposure to estrogens. Little attention has been paid to the immunological effects of 17β-estradiol (E2) and 17α-ethinylestradiol (EE), potent modulators of the immune system. Does exposure to E2 or EE at low concentrations for a subacute duration affect this system? Are the effects similar for both hormones and between genders? Are these effects similar in young and aged mice? These questions were addressed here, where 10 ng kg−1 BW of E2, EE, or vehicle were orally administered every other day for 21 days to young (6-week-old) and aged (>15-month-old) C57BL/6 mice. As expected, significant gender and age-related differences were noted with regard to thymus weight, thymocyte recovery, spleen weight, and splenocyte recovery. However, low dose treatment of E2 or EE produced no marked effects on the thymus or spleen organ to body weight ratios, cell numbers, or lymphocyte subsets. Low dose oral estrogens did not noticeably alter the ability of activated splenocytes to induce interferon-γ or nitric oxide. In summary, our studies of young and aged C57BL/6 mice suggest that low dose subacute exposure to E2 or EE did not markedly affect lymphoid organs (thymus or spleen weight) or lymphocyte subsets.

Effect of sub-acute oral cyanide administration in rats: Protective efficacy of alpha-ketoglutarate and sodium thiosulfate

Chronic toxicity of cyanide in humans and animals has been previously described. Alpha-ketoglutarate (alpha-KG) and sodium thiosulfate (STS) are known to confer remarkable protection against acute cyanide poisoning in rodents. Their efficacy against sub-acute or chronic cyanide exposure is not known. The objective of the present study was to assess the sub-acute toxicity of potassium cyanide (KCN) in female rats following oral administration of 7.0 mg/kg (0.5 LD 50) for 14 d. The effect of alpha-KG (oral; 1.0 g/kg) and/or STS (intraperitoneal, 1.0 g/kg) on cyanide toxicity was also evaluated. Various hematological and biochemical indices were determined after 7 d of treatment and additional parameters like organ-body weight index (OBI) and histology of brain, heart, lung, liver, kidney and spleen were performed after 14 and 21 d (recovery group) of cyanide exposure. Sub-acute exposure of KCN did not produce any significant change in body weight of the animals, OBI, hematology and the levels of blood urea, creatinine, aspartate aminotransferase, triiodothyronine (T3) and tetraiodothyronine (T4). The levels of temporal glutathione disulfide (GSSG) and hepatic malondialdehyde (MDA), reduced glutathione (GSH) and GSSG were unaffected. However, in KCN treated animals elevated levels of blood glucose and reduced levels of alanine aminotransferase were observed. Activities of cytochrome c oxidase in the brain and rhodanese in the liver were diminished. Reduced levels of GSH and enhanced levels of MDA in brain were observed. Increased levels of blood thiocyanate were observed in all the treatments of KCN. Additionally, KCN also produced various histological changes in the brain, heart, liver and kidney. Although, treatment of alpha-KG and STS alone significantly blunted the toxicity of KCN, concomitant use of both interventions afforded to maximum protection. This study indicates a promising role of alpha-KG and STS for the treatment of prolonged cyanide exposures.

Hexanic Maca extract improves rat sexual performance more effectively than methanolic and chloroformic Maca extracts.

Lepidium meyenii (Maca) is traditionally employed in the Andean region for its supposed properties in improving fertility. The aim of this study was to determine the effect of subacute oral administration of hexanic, methanolic and chloroformic extracts of Maca root on sexual performance in inexperienced male rats. The following sexual performance parameters were evaluated: 1st mount, 1st intromission, ejaculation and post-ejaculatory latencies, intercopulatory interval and copulatory efficacy. All the tested fractions significantly decreased intromission latency and intercopulatory interval and increased intromission frequency and copulatory efficacy (P < 0.05) as compared to controls. Hexanic and methanolic extracts were able to increase mount frequency (MF), while only hexanic fraction significantly improved mount latency (ML) (P=0.038). Globally, only the hexanic fraction significantly improved the majority of the sexual parameters measured. Sub-acute oral administration of hexanic Maca extract improved sexual performance parameters in sexually inexperienced male rats most effectively.