Attenuation of CFA-induced arthritis through regulation of inflammatory cytokines and antioxidant mechanisms by Solanum nigrum L. leaves extracts.

Solanum nigrum L. is a popular traditional medicine for various inflammatory conditions including rheumatism and joint pain. The current study aimed to evaluate the anti-arthritic mechanism of Solanum nigrum L. Four extracts were prepared using n-hexane, methanol, chloroform, and water. The anti-nociceptive and anti-inflammatory activity was carried out with 100, 200, and 300 mg/kg body wt. PO of each extract by the hot plate and carrageenan-induced paw oedema methods, respectively. The anti-arthritic study was performed with chloroform and aqueous extracts (300 mg/kg) in complete Freund's adjuvant (CFA)-induced arthritis. Paw size (mm), ankle joint diameter (mm), and latency time (sec) were recorded on day 0 and every 4th day till 28 days. The hematological, inflammatory, and oxidative biomarkers were estimated. Results showed that significant analgesia (p < 0.05) and reduction in paw inflammation were achieved with all extracts. The highest percent inhibition in Carrageenan-induced inflammation was achieved with 300 mg/kg of chloroform (72.19%) and aqueous (71.30%) extracts, respectively. In the CFA model, both extracts showed a significant reduction in paw size and ankle joint diameter (p < 0.05). The RT-qPCR analysis revealed the upregulation of interleukin-4 and interleukin-10, and down-expression of interleukin-1ß, interleukin-6, tumor necrosis factor-α, cycloxygenase-2, nuclear factor-κB, prostaglandin E synthase 2, and interferon-γ. A significant increase in superoxide dismutase, catalase, and glutathione levels was observed. Hence, it is concluded that Solanum nigrum L. leaf extracts regulate the expression of inflammatory markers and improve oxidative stress resulting in the attenuation of CFA-induced arthritis.

Biomolecular Screening of Pimpinella anisum L. for Antioxidant and Anticholinesterase Activity in Mice Brain.

Hundreds of the plants have been explored and evaluated for antioxidant and anti-amnesic activities, so far. This study was designed to report the biomolecules of Pimpinella anisum L. for the said activities. The aqueous extract of dried P. anisum seeds was fractionated via column chromatography and the fractions so obtained were assessed for the inhibition of acetylcholinesterase (AChE) via in vitro analysis. The fraction which best inhibited AChE was so named as the P. anisum active fraction (P.aAF). The P.aAF was then chemically analyzed via GCMS, which indicated that oxadiazole compounds were present in it. The P.aAF was then administered to albino mice to conduct the in vivo (behavioral and biochemical) studies. The results of the behavioral studies indicated the significant (p < 0.001) increase in inflexion ratio, by the number of hole-pokings through holes and time spent in a dark area by P.aAF treated mice. Biochemical studies demonstrated that the oxadiazole present in P.aAF on one hand presented a noteworthy reduction in MDA and the AChE level and on the other hand promoted the levels of CAT, SOD and GSH in mice brain. The LD50 for P.aAF was calculated as 95 mg/Kg/p.o. The findings thus supported that the antioxidant and anticholinesterase activities of P. anisum are due to its oxadiazole compounds.

Clinical efficacy of various anti-hypertensive regimens in hypertensive women of Punjab; a longitudinal cohort study.

BACKGROUND: Gender wise differences exist in anti-hypertensive treatment outcomes, yet still un-explored in Pakistan. Thus, we aimed to estimate the clinical efficacy of four different anti-hypertensive regimens in hypertensive women of Punjab, Pakistan. METHODS: A longitudinal cohort study of 12 months duration was conducted by enrolling 300 hypertensive women on four anti-hypertensive regimens. Chi-square for significance, logistic regression for association and multilevel regression for changes in outcomes were used. RESULTS: Majority of subjects were < 60 years of age, weighing > 65 Kg, having family history, married and hailing from urban areas, with diabetes as the most common comorbidity. Hypertension, adjusted for covariates, was significantly associated with salt intake (OR:2.27, p <  0.01) and physical activity (OR;2.16, p <  0.01). High-risk subjects, compared to low-risk, were consuming more fat (OR;1.54), meat (OR; 2), salt (OR; 2.48) and even vegetables/fruits (OR;3.43). Compared to baseline, the maximum reduction in BP was observed with combination therapy, N-GITS+LTN + HCT (SBP; - 50.17, p <  0.01, DBP; - 16.55, p <  0.01), followed by N-GITS alone (SBP; - 28.89, p <  0.01, DBP; - 12.21, p <  0.01). Compared to baseline, adjusted for treatment effects, significant reductions in SBP (low-risk; - 17.92, p <  0.01 high-risk; - 19.48, p <  0.01) and DBP (low-risk; - 17.92, p <  0.01, high-risk; - 19.48, p <  0.01) were observed in low and high risk patients. Among all four cohorts, orthostatic hypotension and edema were common in N-GITS+LTN + HCT only, but variable effects were observed on biochemical values; urea, BSR and creatinine. CONCLUSION: In conclusion, compared to a single agent, combination therapy conferred improved BP controls followed by N-GITS alone in low and high risk women with manageable side effects.

Is folklore use of Euphorbia helioscopia devoid of toxic effects?

OBJECTIVE: To evaluate acute toxic effects of Euphorbia helioscopia in order to assure the safety and usefulness of herbal remedy. MATERIALS AND METHODS: The Organization for Economic Cooperation and Development (OECD) for chemical testing guidelines No. 425 for acute oral toxicity testing were followed in this study. Mice were divided into three groups (n = 5). Group I served as control. Groups II and III were administered methanol extract of E. helioscopia leaves and latex orally at dose of 2000 mg/kg, respectively. Then, all the animals were observed for two weeks. Blood sampling was done by cardiac puncture after 14 days from each group for biochemical analysis. Histopathology was performed to find out any microscopic lesion in vital organs. RESULTS AND DISCUSSION: LD50 was found greater than 2000 mg/kg. There was decrease in cholesterol, triglycerides, LDL and VLDL levels of latex and leaves with methanol extract-treated animals, with respect to control indicating plant's hypolipidemic effect. On macroscopic examination, no lesions were found on vital organs, such as liver, heart and kidney; and normal architecture was observed on microscopic examination. CONCLUSION: On the basis of results, it was concluded that methanol extract of E. helioscopia leaves and latex were devoid of toxic effects in acute toxicity study.

Impairment of liver synthetic function and the production of plasma proteins in primary breast cancer patients on doxorubicincyclophosphamide (AC) protocol.

Doxorubicin and Cyclophosphamide (AC protocol) combination is usually considered as a first line therapy in newly diagnosed breast cancer patients. Thus, a retrospective observational study was conducted to monitor the effect of AC protocol on liver synthetic functions and production of plasma proteins in breast cancer patients, reporting to specialized cancer care hospital of Lahore, Pakistan. A total of 75 patients (n=75) on AC protocol with breast cancer were observed in this study. The patient data including age, gender, body surface area, dosage, disease status and laboratory biochemical values were recorded by reviewing historical treatment records. Pre-treatment values were taken as baseline values for albumin, globulin, blood urea nitrogen (BUN), albumin/globulin (A/G) ratio and total proteins. The baseline values were compared after each cycle of by applying ANOVA using statistical tool SPSS® version 21. The plasma levels of blood urea nitrogen (BUN), total protein and globulin dropped significantly (p<0.05) in patients of all age groups. However, the albumin levels were not significantly changed (p>0.05). The A/G ratio level increased (p<0.05) as a result of reduction in globulin levels. Significant changes in plasma protein levels were observed in the elderly patients (50 to 65 years) than patients between 20 to 50 years of age. AC protocol impairs liver synthetic functions as observed by decreased blood urea nitrogen (BUN) and plasma protein levels.

Protective effect of crude Curcuma longa and its methanolic extract in alloxanized rabbits.

Curcuma longa (C. longa) is commonly found in different areas of Pakistan. It has been locally utilized as a traditional medicine. The aim of this study was to evaluate the antidiabetic, hepatoprotective and total antioxidant effect of the crude drug and its methanolic extract in rabbits. Diabetes was induced with alloxan (180mg/kg). Two major groups were designed, curative and protective groups. In curative group the crude drug and its methanolic extract was orally administered to the diabetic animals and acute study was performed. On the other hand in protective group the crude drug and its methanolic extract were administered for eight days prior to the diabetes induction. Results indicated that in Curative group the crude and methanolic extract of C. longa significantly improved the levels of serum glucose, serum transaminases and antioxidant activity (AOA). In protective group, serum glucose, serum transaminases were not significantly increased by alloxan, in both crude as well as methanolic extract group. This study shows that C. longa acts as antidiabetic, hepatoprotective and antioxidant in diabetes especially type 1 diabetes.

Report: physicochemical and phytochemical analysis of Euphorbia helioscopia (L.).

The present study aimed to standardize the crude drug from "Euphorbia helioscopia" by doing qualitative and quantitative analysis of different pulverized plant parts and extracts. Physicochemical analysis (determination of moisture contents, total ash, water insoluble ash, sulphated ash, acid insoluble ash, and water and alcohol extractives) was done on powdered raw materials (stem and leaves). The moisture contents and the ash value were found within the normal recommended range (moisture contents 6% and ash value 20%). The value of water-soluble extracts was higher as compared to alcohol soluble extractives. Percentage yield was highest in methanol solvent. The phytochemical analysis i.e. total lipids, total proteins and carbohydrates of crude powder showed that lipids and proteins contents were high (2.4% & 0.91% respectively) in pulverized stem while carbohydrate contents were high (78.27%) in pulverized leaves. Qualitative analysis by FTIR fingerprints and UV-scanning showed that stem and leaves of the plant contained the same constituents because their spectra are super-imposable. Aqueous-, ethanol-, petroleum ether-, chloroform- and methanol extracts were used in the study. Quantitative analysis was done by calculating the primary and secondary metabolites (total proteins, total glycosaponins, total alkaloids, total flavonoids, and total polyphenolics) in all the extracts using suitable markers. Chloroform gave very less percentage yield and nil primary metabolites so it was eliminated from secondary metabolites estimation. The maximum value of total proteins, total glycosaponins, total alkaloids, total flavonoids and total polyphenolics were found in the leaves methanol (36.56%), stem methanol (34%), stem ethanol (41.84%), leaves methanol (108.96%), and leaves petroleum ether (7.22%) respectively. Different pharmacological activities of the plants are due to their flavonoid contents. It is concluded that methanol is the best solvent for extraction. Any arial part of the plant can be used in pharmacological evaluations prior to pre-clinical and clinical studies because leaves and stem had superimposable spectra in FTIR and UV-scanning.

Biomolecular Evaluation of Lavandula stoechas L. for Nootropic Activity.

Lavandula Stoechas L. is widely known for its pharmacological properties. This study was performed to identify its biomolecules, which are responsible for enhancement of memory. L. stoechas aqueous extract was first purified by liquid column chromatography. The purified fractions were analyzed for in vitro anti-cholinesterase activity. The fraction that produced the best anti-cholinesterase activity was named an active fraction of L. stoechas (AfL.s). This was then subjected to GC-MS for identifications of biomolecules present in it. GC-MS indicated the presence of phenethylamine and α-tocopherol in AfL.s. Different doses of AfL.s were orally administered (for seven days) to scopolamine-induced hyper-amnesic albino mice and then behavioral studies were performed on mice for two days. After that, animals were sacrificed and their brains were isolated to perform the biochemical assay. Results of behavioral studies indicated that AfL.s improved the inflexion ratio in mice, which indicated improvement in retention behavior. Similarly, AfL.s significantly (p < 0.001) reduced acetylcholinesterase and malondialdehyde contents of mice brain, but on the other hand, it improved the level of choline acetyltransferase, catalase, superoxide dismutase, and glutathione. It was found that that high doses of AfL.s (≥400 mg/Kg/p.o.) produced hyper-activity, hyperstimulation, ataxia, seizures, and ultimate death in mice. Its LD50 was calculated as 325 mg/Kg/p.o. The study concludes that α-tocopherol and phenethylamine (a primary amine) present in L. stoechas enhance memory in animal models.

Comparison of clinico-pathological characteristics and survival of recurrent ovarian cancer patients on seven different chemo-protocols.

Despite growing prevalence of ovarian cancer (OC) in Pakistan, no literature evidence exists regarding its clinic-pathological characteristics, survival and compliance of patients with recurrent ovarian cancer on various chemo-protocols. An observational study was conducted by enrolling 251 recurrent OC patients on 7 different chemo-protocols, from a specialized cancer care hospital, Lahore, Pakistan, using convenient judgmental sampling. The study was conducted for a period of 6 months. Most of the patients were between 18 and 70 years of age, with IIIC FIGO stage and papillary serous histological grade. As per RECIST, improved partial response (PR) (63.3 %) and complete response (CR) (52.1 %) was observed in the CP (carboplatin + paclitaxel) arm, substantiated by improved median progression free survival (PFS) and overall survival (OS) in CP and CD (carboplatin + docetaxel) arms, respectively, yet with no significant differences in survival curves, PFS (p = 0.12) and OS (p = 0.22). Interestingly, the highest and the lowest patient non-compliance were observed in CG (carboplatin + gemcitabine) (81.6 %) and paclitaxel (4.5 %) arms, resp. As per the hazard model for survival, topotecan showed significant association with the therapy related events/deaths compared to other protocols. These data suggest that CP regimen exhibited improved clinical efficacy and decreased toxicity related non-compliance in recurrent ovarian cancer patients of Lahore.

Post-surgical antibiotic prophylaxis: Impact of pharmacist's educational intervention on appropriate use of antibiotics.

BACKGROUND: Guidelines assisted appropriate use of prophylactic antibiotics can lower the prevalence of surgical site infections (SSIs). The present study was conducted to evaluate the impact and cost-benefit value of pharmacist's educational intervention for antibiotic use in post-surgical prophylaxis. METHODS: A prospective quasi experimental study was conducted by enrolling 450 patients from tertiary care hospital of Lahore, Pakistan, 225 patients in each, control and intervention, arm using non-random convenient sampling. The study parameters included antibiotic indication, choice, dose, frequency, duration and associated costs. This study is registered with Chinese Clinical Trial Registry # ChiCTR-OON-17013246. RESULTS AND CONCLUSION: After educational intervention, in post-intervention arm, total compliance in terms of correct antibiotic choice, dose, frequency and duration increased from 1.3% to 12.4%. The rate of inappropriate antibiotic choice did not change significantly. After intervention only metronidazole utilization decreased (16%) significantly (p=0.011). Significant reductions were observed in mean duration of antibiotic prophylaxis (17%, p=0.003), average number of prescribed antibiotics (9.1%, p=0.014) and average antibiotic cost (25.7%, p=0.03), with reduction in mean hospitalization cost (p=0.003) and length of stay (p=0.023). Educational intervention was significantly associated (OR; 2.4, p=0.005) with appropriate antibiotic prophylaxis. The benefit of pharmacist intervention, mean antibiotic cost savings to mean cost of pharmacist time, was 4.8:1. Thus, the educational intervention resulted in significant reductions in the duration and average number of antibiotic use having considerable effect on therapy and hospitalization cost.

Lavandula stoechas (L) a Very Potent Antioxidant Attenuates Dementia in Scopolamine Induced Memory Deficit Mice.

The objective of the current project was to explore the pharmacotherapeutic role of Lavandula stoechas (L) for the management of dementia. Dementia is considered a global challenge of current century seeking special attention of pharmacologists to explore its best remedies. Methanolic extract of aerial parts of L. stoechas was tested for phytochemical analysis along with free radical scavenging activity. Behavioral studies were performed on scopolamine induced amnesic mice by using elevated plus maze (EPM), light and dark test and hole board paradigms. Biochemical investigations were made after decapitating the mice. Their brains were isolated for biochemical estimation of acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Phytochemical study ensured the presence of total phenolic contents (285.91 ± 0.75 mg of GAE/g of extract), total flavonoids (134.06 ± 0.63 mg of RE/g of extract), total tannins (149.60 ± 0.93 mg of TAE/g of extract) and free radical scavenging activity (IC50 value = 76.73 µg/ml found by DPPH method). Behavioral studies indicated that animals of GVII showed higher inflexion ratio (0.40 ± 0.03) for EPM, spent most of time (227.17 ± 2.13 s) in dark area of light dark test and had many hole pockings (39.83 ± 1.88) for hole board paradigm. Moreover, biochemical studies revealed that methanolic extract of L. stoechas (800 mg/kg/p.o.) significantly (P < 0.001) reduced brain AChE and MDA levels while improved SOD, CAT, and GSH levels. Thus the findings suggest that L. stoechas stabilizes memory by enhancing cholinergic neurotransmission and by providing defense against oxidative stress in mice brain.

Efficacy and Tolerability of Antihypertensive Drugs in Diabetic and Nondiabetic Patients.

OBJECTIVES OF THE STUDY: The aim of the study was to compare the efficacy and tolerability of different classes of antihypertensive drugs in diabetic and nondiabetic patients (NDPs) with essential hypertension. MATERIAL AND METHODS: The study was conducted in Mayo Hospital, Punjab Institute of Cardiology, and National Defence Hospital, Lahore, Pakistan, on 200 hypertensive patients with diabetes and 230 hypertensive patients without (Three hospitals) diabetes. Both male and female patients of age between 30 and 80 years with systolic blood pressure (SBP) above 130 mmHg and diastolic blood pressure (DBP) above 80 mmHg were enrolled in the study. Angiotensin converting enzyme inhibitors (ACEI), beta-blocker (ßB), calcium-channel blocker (CCB), diuretics (D), angiotensin receptor blocker (ARB) as well as α-blocker classes of antihypertensive drugs were used. These drugs were used as monotherapy as well as combination therapy. The study was conducted for 4 months (July-October). After 4 months, patients were assessed for efficacy by monitoring blood pressure (BP) and tolerability by assessing safety profile on renal function, liver function as well as lipid profile. RESULTS: Significant control in mean BP by all drug groups was observed in "both groups that is patients with diabetes and without diabetes." The efficacy and tolerability data revealed that in diabetic patients with hypertension, the highest decrease in SBP and DBP was observed using monotherapy with ACEI, two-drug combination therapy with ACEI plus diuretic, ARBs plus diuretic, ACEI plus CCBs, three-drug combination therapy with ACEI plus CCBs plus diuretic, and four drug combination therapy with ACEI plus CCBs plus diuretic plus ßBs, ARB's plus CCBs plus diuretic plus ßBs while in NDPs, monotherapy with diuretic, two-drug combination therapy with ACEI plus CCBs, ACEI plus ßBs, three-drug combination therapy with ßBs plus ACEI plus D was found more effective in controlling SBP as well as DBP. Adverse effects observed were dry cough, pedal edema, dizziness, muscular cramps, constipation, palpitations, sweating, vertigo, tinnitus, paresthesia, and sexual dysfunction. CONCLUSION: All classes of antihypertensives were found to control blood pressure significantly in both groups of patients that is diabetic patients with hypertesion and non-diabetic patients with hypertension.

Antibiotic Self-Prescribing Trends, Experiences and Attitudes in Upper Respiratory Tract Infection among Pharmacy and Non-Pharmacy Students: A Study from Lahore.

Pharmacists are the custodians of drugs; hence their education, training, behaviors and experiences would affect the future use of drugs at community and hospital pharmacies. Therefore, we aimed at evaluating the self-prescribing antibiotic trends, knowledge and attitudes among pharmacy and non-pharmacy students. We found that pharmacy students had higher risks of experiencing URIs related symptoms such as cough (RR; 1.7, p = 0.002), allergy (RR; 2.07, p = 0.03) and running nose (RR; 3.17, p<0.005), compared to non-pharmacy students -resulting in higher probabilities of selecting cough syrups (OR; 2.3, p<0.005), anti-histamines (OR; 1.8, p = 0.036) and anti-inflammatory/anti-pyretic (OR; 2.4, p<0.005) drugs. Likewise, bachelor's degree pupils (OR; 2, p = 0.045), urban area residents (OR; 2.44; p = 0.002) and pharmacy students (OR; 2.9, p<0.005) exhibited higher propensities of antibiotic self-use-notable classes include, b-lactams (45.9%) followed by macrolides (26.5%) and augmentin (28.94%), respectively. Surprisingly, pharmacy and non-pharmacy students had higher odds of using antibiotics in common cold (OR; 3.2, p<0.005) and pain (OR; 2.37, p = 0.015), respectively. Unlike non-pharmacy students, pharmacy students were likely to select alternative therapy, such as Joshanda (OR; 2.22, p = 0.011) and were well acquainted with antibiotic hazards, with 77% reduction in risk of antibiotics re-use. In conclusion, university students exhibited antibiotic self-prescribing trends in conditions that does not warrant their use, thus are irrational users. The pharmacy education confers very little benefit to rational self-prescribing practices among students, while non-pharmacy students are more vulnerable to repeated antibiotic usage. Thus, the educational and training modules should be designed for university students to disseminate targeted information regarding the potential hazards of antibiotic self-use and importance of consultation with qualified and registered medical doctor/pharmacist before starting with antibiotics.

Investigation of in vivo antioxidant activity of Euphorbia helioscopia latex and leaves methanol extract: a target against oxidative stress induced toxicity.

OBJECTIVE: To evaluate in vivo antioxidant activity of latex and leaves methanol extract of Euphorbia helioscopia using mice as experimental animals. METHODS: The plant was collected, identified, dried under shade, ground to fine powder and extraction was done. Latex was collected in dried bottles by cutting the stem. Oxidative stress was induced in mice with acute toxic dose of paracetamol administered intrperitoneally. Latex and leaves methanol extract (600 and 1 200 mg/kg) orally, once a day, were given to mice for two weeks. Then oxidative stress biomarkers were measured in tissue homogenates and serum. RESULTS: Leaves methanol extract exhibited prominent in vivo antioxidant effect as compared to latex. Results showed significant rise in antioxidant enzymes (catalase, superoxide dismutase and glutathione) levels at 1 200 mg/kg dose of extract. Thus, extract helped to detoxify the free radicles by increasing antioxidant enzymes levels. Malondialdehyde value decreased significantly with extract (1 200 mg/kg) which was indicator of extract's power to inhibit the generation of free radicals. Extract (1 200 mg/kg) exhibited maximum cure against stress induced changes in liver, kidney, lipid profile parameters and complete blood count. CONCLUSIONS: Leaves methanol extract of Euphorbia helioscopia raised antioxidant enzymes levels in mice. It showed hepatorenal-curative effect, hypolipidemic effect and hemostasis potential. Thus, it can help the biological systems to fight against stress induced pathological conditions.

Study on cytochrome p-450 dependent retinoic Acid metabolism and its inhibitors as potential agents for cancer therapy.

The relative lack of clinical success with conventional anticancer agents may be due in part to the traditional concept of cancer being a biological state rather than a dynamic process. Redefining cancer as a dynamic disease commencing with carcinogenesis introduces the possibility of chemoprevention. Retinoids offer the promise of a therapeutic option based on differentiation of premalignant as well as malignant cells. Research to date has concentrated on the use of exogenous retinoids in cancer. Although this research continues with new retinoid derivatives, an alternative approach to overcoming the drawbacks associated with exogenous retinoids has been to increase the levels of endogenous retinoic acid (RA) by inhibiting the cytochrome P450- mediated catabolism of RA using a novel class of agents known as retinoic acid metabolism blocking agents (RAMBAs which increase the level of endogenous retinoic acid (RA) within the tumor cells by blocking their metabolism. This approach presents several theoretic advantages.In the present study a wide range of established P-450 inhibitors has been screened to examine their inhibitory activity on all-trans-Retinoic acid (ATRA) metabolism. Forty-one known P450 inhibitors were tested for their inhibitory activity against RA metabolism. Most of them are nitrogen-containing compounds. The results showed that among these compounds only six compounds (N-benzyl-2-phenylethanamine, itraconazole, chlorpromazine, 5-chloro-1,3-benzoxazol-2-amine, proadifen and furazolidone) showed inhibition of RA metabolism which was > 50%. Ketoconazole and liarozole were also screened as standard potent inhibitors in the same system and gave 87.5% and 89% inhibition, respectively. The results indicate that mostly azoles with substituents in positions other than the 1-position on the ring are very weak inhibitors of RA metabolism. The most effective inhibitors (ketoconazole, itraconazole, bifonazole and clotrimazole) are 1-substituted and possess relatively large aromatic groups in the molecule. 1-Substituted imidazoles bind to cytochrome P-450 with a very high affinity but substitution in the other position of the imidazole decreases the binding affinity.

Effects of losartan on blood pressure, oxidative stress, and nitrate/nitrite levels in the nitric oxide deficient hypertensive rats.

Losartan, an angiotensin II type-1 receptor (AT1) antagonist, was used to investigate whether it can offer protection against the sustained hypertension, cardiac hypertrophy, and renal damage induced by chronic inhibition of nitric oxide (NO) by Nomega-nitro-L-arginine methyl ester (L-NAME). We studied the involvement of both NO metabolism and oxidative stress in L-NAME-induced hypertension, and how AT1 receptor antagonism may interact. Male Wistar albino rats were subjected to NO synthesis inhibition by the use of L-NAME (60 mg/kg/day), and the effects of losartan (10 mg/kg/day) in drinking water for six weeks were observed. After six weeks, animals were subjected to the measurements for systolic, mean, and diastolic blood pressure (BPs, BPm, and BPd, respectively). Under light ether anesthesia blood was withdrawn for ACE activity, NOx and creatinine determinations. Heart and kidneys were weighed, and organ indices were calculated comparing to their body weights. These tissues were immediately preserved for GSH, MDA, NOx estimations. Chronic L-NAME treatment raised BPs, BPm, and BPd, respectively, above the normal. Treatment also increased NOx in plasma, significantly decreased it in the heart, and tended to increase it in kidney. L-NAME caused GSH depletion in the heart and kidney tissues with a concomitant increase in MDA contents in both the tissues. Plasma creatinine doubled in L-NAME-treated animals. Plasma ACE activity showed a nonsignificant decrease below control. Concurrent treatment with losartan almost completely inhibited any rise in blood pressure. Losartan replenished the partly depleted cardiac and renal antioxidant GSH and ameliorated the increase of oxidative stress damage index, MDA. However, losartan alone did not change appreciably the plasma level or cardiac and renal contents of NO,. Losartan plus L-NAME treatment caused an increase in plasma ACE activity above control. Furthermore, losartan ameliorated the L-NAME induced increase in creatinine back to value nonsignificantly different from control.