Pioglitazone improves serum lipid profile in diet induced hyperlipidaemic non diabetic rats.

OBJECTIVE: To evaluate the anti-dyslipidaemic effects of pioglitazone in diet-induced non-diabetic hyperlipidaemic rats and to compare them with gemfibrozil. METHODS: This comparative animal study was conducted at the Postgraduate Medical Institute, Lahore, Pakistan, from July to September 2011, and comprised Sprague Dawley albino rats divided into three equal groups. Initially all three groups were given high-lipid diet containing cholesterol 1.5g, coconut oil 8ml and sodium cholate 1.0g per 100g of rat chow to induce hyperlipidaemia. From 4th to 8th week, Group A (control) was given 0.5ml of distilled water, Group B was given pioglitazone 10mg/kg body weight, and Group C was given gemfibrozil 10mg/kg body weight as single morning dose by oral route for a period of 04 weeks in addition to hyperlipidaemic diet. Serum lipid levels were estimated at zero, 4th and 8th week. Blood sugar level was estimated at 4th week to exclude diabetic rats.SPSS 17 was used for data analysis. RESULTS: Of the 27 rats, each group had 9(33.33%) rats. At the start of the study, the mean weight was 254.44±14.67g in Group A, 255.11±14.66g in Group B and 252.22±14.18g in Group C. It was 352.22±16.79g, 332.22±17.19 and 328.11± 12.92 at the 8th week. The mean total cholesterol at 0 week was 71.4±4.88 mg/dl in Group A, 71.9±7.03 in Group B and 73.4±5.27 in Group C. At the 8th week, the values were 161.8±9.2 mg/dl, 100.8±7.0 and 95.0±6.6. The mean low-density lipoproteincholesterol levels in the respective groups were 30.2±4.9mg/dl, 32.2±7.0 and 33.6±6.0 at 0 week; 77.8±8.4, 85.1± 15.3 and 86.9± 6.3 at the 4th week and 113.9± 10.1, 60.4± 9.2 (p< 0.001) and 54.8± 6.6 (p< 0.001) at the 8th week.The mean serum high-density lipoprotein cholesterol at the 8th week was 11.4± 1.7 mg/dl, 19.7± 2.4 (p< 0.001) and 19.2± 2.5 (p< 0.001) in the three groups, respectively. CONCLUSIONS: Treatment with pioglitazone improved serum lipid profile of non-diabetic hyperlipidaemic rats equivalent to that of gemfibrozil.

Anti inflammatory effect of thymoquinone in comparison with methotrexate on pristane induced arthritis in rats.

OBJECTIVE: To determine the anti-inflammatory effects of thymoquinone on body weight, clinical score of inflammation, total leukocyte count and differential leukocyte count in arthritic rats and compare it with that of methotrexate. METHODS: The study was conducted at the Post-Graduate Medical Institute, Lahore, from March to September 2013, and comprised female Sprague-Dawley rats randomised into four equal groups; group A (healthy control), group B (positive control), group C (thymoquinone treated) and group D (methotrexate treated). Arthritis developed in Group B, C and D within two weeks after a single intra-dermal injection of pristane. Body-weight measured on electronic balance in grams and clinical score of inflammation scored on macroscopic scoring system were monitored on every alternate day while total leukocyte count and differential leukocyte count were taken at day 0, 16 and 30. After day 15, groups A and B were given 0.5ml of distilled water by intra-peritoneal injection daily for 15 consecutive days; group C was given thymoquinone 2mg/kg by intra-peritoneal injection daily for 15 consecutive days, and group D received methotrexate 0.5mg/kg by intra-peritoneal injection, daily for 15 consecutive days. SPSS 20 was used for statistical analysis. RESULTS: The 32 rats in the study were randomised into four groups of 8(25%) each. In group A the body-weight continued to increase and reached a mean of 144.13±10.8% of the baseline at day 30. In group B the weight reduced to 93.13±4.19% at day 16 and to 88.3±6.97% at day 30. In groups C and D the weight reduced to 87.25±7.69% and 88.5±7.07% respectively at day 16; then the animals in the two groups regained their weight which increased to 108.63±10.89% and 103.38±6.25% respectively at day 30. The score was zero in group A throughout the study period. The score of group B, which was zero at day 0, reached a mean of 16±0 at day 16. In groups C and D, the mean score increased till day 16 and reached 16±1 and 16±0 respectively, and then reduced to 5±2 and 4±1 at day 30 respectively. CONCLUSIONS: Evaluation of data supported the anti-inflammatory activities of thymoquinone, so it may be investigated as an effective anti-inflammatory drug in rheumatoid arthritis.

IN VITRO ACTIVITY OF VACCINIUM MACROCARPON (CRANBERRY) ON URINARY TRACT PATHOGENS IN UNCOMPLICATED URINARY TRACT INFECTION.

BACKGROUND: Urinary tract infection is the most common bacterial infection in the community, mainly caused by Escherichia coli (E coli). Due to its high incidence and recurrence, problems are faced in the treatment with antibiotics. Cranberry being herbal remedy have long been the focus of interest for their beneficial effects in preventing urinary tract infections. This study was conducted to analyse in vitro activity of cranberry (Vaccinium macrocarpon) on uropathogenic E coli in uncomplicated urinary tract infections. METHODS: In this laboratory based single group experimental study, anti-bacterial activity of Vaccinium macrocarpon concentrate on urinary tract E coli was investigated, in vitro. Ninety-six culture positive cases of different uropathogens were identified. Vaccinium macrocarpon concentrate at different concentrations was prepared in distilled water and put in wells punched in nutrient agar. E coli isolates were inoculated on the plates and incubated at 37 °C for 24 hours. A citric acid solution of the same pH as that of Vaccinium macrocarpon was used and put in a well on the same plate to exclude the effect of pH. RESULTS: A total of 35 isolates of E coli were identified out of 96 culture positive specimens of urine and found sensitive to Vaccinium macrocarpon (p<0.000). Results revealed that Vaccinium macrocarpon has antibacterial effect against E coli. Furthermore the antibacterial activity of Vaccinium macrocarpon has dose response relationship. Acidic nature of Vaccinium macrocarpon due to its pH is not contributory towards its antibacterial effect. CONCLUSION: Vaccinium macrocarpon concentrate may be used in urinary tract infection caused by E coli.

Effect Of Justicia Adhatoda (Malabar Nut) Leaf Extract On Drug-Induced Coagulopathy In Mice And In-Vitro Platelet Aggregation Of Human Blood.

BACKGROUND: Justicia adhatoda is widely used in traditional medicine for treatment of menorrhagia, piles and bleeding disorders. Oral antiplatelet and anticoagulant drugs are routinely prescribed to patients with cardiovascular diseases. These drugs have one major adverse effect that they can cause spontaneous haemorrhage, which can be fatal. Development of a haemostatic agent can help in effective management of drug-induced haemorrhages. This study was devised to observe the effect of leaf extract of Justicia adhatoda on coagulation profile in mice and to evaluate its effect on in-vitro platelet aggregation. METHODS: The study was divided into two parts. First part was designed to evaluate the effect of J. adhatoda leaf extract on coagulation parameters. Three drugs were used to induce coagulopathy viz., warfarin, aspirin and dabigatran. Bleeding time, platelet count, PT and APTT were estimated. Second part of this study was devised to observe the effect of J. adhatoda leaf extract on in vitro platelet aggregation of human. Percent aggregation was recorded by light transmission aggregometer for three minutes. RESULTS: Leaf extract of Justicia adhatoda decreased bleeding time from 6.1±2.36 minutes in normal control to 1.9±1.03 minutes in extract treated mice. There was no effect on the coagulation parameters. Platelet count increased significantly only in the aspirin treated group that received the extract to 540±46.8x103 /µl from 436.9±37.9x103 /µl of aspirin treated group. Platelet aggregation in vitro increased in a dose dependent manner. CONCLUSION: Justicia adhatoda leaf extract is effective in controlling excessive bleeding in vivo, in mice with acquired platelet defect produced by aspirin. This haemostatic effect is probably due to increased platelet aggregation as indicated by the in vitro results.

Hepatoprotective Effect Of Prazosin Is Comparable To N-Acetylcysteine In Acetaminophen Induced Hepatotoxicity In Mice.

BACKGROUND: Autonomic nervous system modulates acetaminophen induced hepatotoxicity. The purpose of the study was to determine the hepatoprotective effect of α1 antagonist (prazosin) and ß2 agonist (salbutamol) on acetaminophen induced hepatotoxicity in mice. METHODS: This experimental study was conducted at Post Graduate Medical Institute, Lahore in which 50 adult mice were divided in to five groups. With the exception of normal control, hepatotoxicity was induced in all other study groups by giving single intraperitoneal injection of acetaminophen 300 mg/ kg. First and second groups served as normal and toxic control were given distilled water 6 ml/ kg while third, fourth and fifth experimental groups were given N-acetylcysteine (300 mg/ kg), prazosin (0.18 mg/ kg) and salbutamol (0.35 mg/kg) intraperitoneally at 2,4 and 8 hours after acetaminophen injection. Serum liver enzymes were analysed at 0 and 72 hours while histopathological finding were assessed at the end of study by using SPSS-20. RESULTS: All the groups treated with toxic dose of acetaminophen showed significant increase in serum ALT, i.e., B (Toxic control 3372%), C (NAC treated 282%), D (Prazosin treated 582%), E(Salbutamol treated 3297%) and AST levels, i.e., B (Toxic control 2750% ), C (NAC treated 230% ), D (Prazosin treated 280%), E (Salbutamol treated 828%) with p-value ˂0.001. When this increase was compared between groups, the lowest increase in serum ALT and AST levels was observed in Nacetylcysteine and prazosin group with no significant difference. Similarly, experimental animals receiving prazosin and N-acetylcysteine had the lowest inflammation, degeneration and necrosis scores than the toxic control group in histopathological analysis of the liver with p-value <0.001. CONCLUSIONS: The hepatoprotective effect of prazosin is comparable to N- acetylcysteine against acetaminophen induced hepatotoxicity in mice.

Effect Of Three Pakistani Date-Seed Varieties On Lipid Profile Of Diet Induced Hyperlipidemic Rabbits.

BACKGROUND: Hyperlipidemia is one of the major risk factors of cardiovascular diseases. In addition to current therapeutic strategies, a lot of work is being done on nutraceutical management of this condition. This study was designed to assess the effect of date seed powder on lipid profile of diet induced hyperlipidemic rabbits. METHODS: Thirty male rabbits were divided into five groups, having six animals in each. One group was given normal rabbit chow throughout the study period of eight weeks. The remaining four groups were fed high fat diet (4% coconut oil and 1% cholesterol powder) for first four weeks in order to induce hyperlipidemia. After first four weeks, 2% date seed powder of three Pakistani varieties namely Dhakki, Khudrawi and Desi was added to the diet of three experimental hyperlipidemic groups for the next four weeks. Body weight and blood samples were taken at zero, 4th and 8th week of study. Serum was analyzed for total cholesterol, LDL-cholesterol, HDL-cholesterol and serum triglycerides. LDL/HDL ratio and AIP were calculated. RESULTS: It was observed that date seed powder of the three varieties significantly decreased total cholesterol, serum triglycerides and AIP. There was no significant change in body weight, HDL-cholesterol, and LDL/HDL ratio. LDL cholesterol was decreased significantly only by Khudrawi date seed powder. CONCLUSIONS: It was concluded that date seed powder has marked antihyperlipidemic properties. However, the difference in appearance, taste and price of different dates does not affect their lipid lowering capacity.

Anti-Arthritic Effect Of Thymoquinone In Comparison With Methotrexate On Pristane Induced Arthritis In Female Sprague Dawley Rats.

BACKGROUND: Rheumatoid arthritis inflammatory joint disease which is chronic in nature. Since long various researches are carried out to find the remedy of this disease but still a lot of work needed to be done. METHODS: This comparative study was performed from March to August 2013 at Postgraduate Medical Institute, Lahore. A total of thirty-two female Sprague-Dawley rats were randomly divided into four equal groups (n=8); group A was kept as healthy control, group B was kept as positive control, group C was treated with thymoquinone and group D was treated with methotrexate. Arthritis developed within two weeks in group B, group C and group D after giving a single shot of pristane intradermally. Treatment was started on day 15. At day 30 (time of dissection) paw weight and histopathological sections of ankle joints of all the animals were taken. RESULTS: The results shown significant rise in paw weight and score of histopathological parameters in group B, group C and group D when compared with healthy control rats. Thymoquinone and methotrexate treated groups shown reduction in paw weight and score of histopathological parameters when compared to positive control rats with p-value 0.001each. The difference between groups C and D was insignificant (p-value 0.062). CONCLUSIONS: Study results supported the anti-inflammatory and disease modifying activities of thymoquinone as it significantly reduces both paw weight and histological parameters of joint inflammation.