Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 67
Filter
Add more filters

Country/Region as subject
Publication year range
1.
Pak J Med Sci ; 40(8): 1765-1769, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39281240

ABSTRACT

Background & Objectives: Ataxia is usually caused by cerebellar pathology or a decrease in vestibular or proprioceptive afferent input to the cerebellum. It is characterized by uncoordinated walking, truncal instability, body or head tremors, uncontrolled coordination of the hands, dysarthria, and aberrant eye movements. The objective of the current investigation was to identify the underlying genetic cause of the hereditary ataxia that affects the Pakistani population. Methods: We studied numerous consanguineous Pakistani families whose members had ataxia-related clinical symptoms to varying degrees. The families were chosen from the Punjab province, and the neurophysician conducted a clinical examination. Peripheral blood samples from both sick and healthy members of the family were taken after obtaining informed consent. Genomic DNA was used to find potential variations in probands using whole exome sequencing. The study was carried out at the University Hospital of Tübingen, Germany, and Government College University in Faisalabad, Pakistan, during 2018-2023. Results: The molecular analysis of these families identified different variants including SGCB: c.902C>T, c.668G>A, ATM: c.6196_6197insGAA, SPG11: c.5769del, SETX c.5525_5533del, and ATM: c.7969A>T. A noteworthy mutation in ATM and SETX was observed among them, and its symptoms were shown to cause ataxia in these families. Conclusion: The current study broadens the mutation spectrum of several hereditary ataxia types and suggests the next generation sequencing in conjunction with clinical research for a more accurate diagnosis of overlapping phenotypes of this disorder in the Pakistani population.

2.
Toxicol Appl Pharmacol ; 471: 116559, 2023 07 15.
Article in English | MEDLINE | ID: mdl-37217007

ABSTRACT

Polystyrene microplastics (PS-MPs) are the potential environmental pollutants that possess the ability to induce testicular damage. Astilbin (ASB) is a dihydroflavonol, abundantly reported in multiple plants that has various pharmacological properties. This research elucidated the mitigative potential of ASB against PS-MPs-instigated testicular toxicity. 48 adult male rats (200 ± 10 g) were distributed into 4 groups (n = 12): control, PS-MPs received (0.01 mg/kg), PS-MPs + ASB received (0.01 mg/kg + 20 mg/kg) and ASB supplemented group (20 mg/kg). After 56th day of the trial, animals were sacrificed and testes were harvested for the estimation of biochemical, hormonal, spermatogenic, steroidogenic, apoptotic and histological profiles. PS-MPs intoxication significantly (P < 0.05) lowered glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione reductase (GSR) as well as catalase (CAT) activities, whereas elevated MDA as well as ROS levels. Besides, the levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), nuclear factor kappa-B (NF-κB) along with cyclooxygenase-2 (COX-2) activity were raised. PS-MPs treatment reduced luteinizing hormone (LH), plasma testosterone and follicle-stimulating hormone (FSH) level besides decreased epididymal sperm number, viability, motility as well as the count of HOS coil-tailed spermatozoa and increased sperm morphological irregularities. PS-MPs exposure lowered steroidogenic enzymes (17ß-HSD, 3ß-HSD and StAR protein along with Bcl-2 expression, besides increasing Caspase-3 and Bax expressions and histopathological alterations in testicular tissues. However, ASB treatment significantly reversed PS-MPs mediated damage. In conclusion, ASB administration is protective against PS-MPs-instigated testicular damage owing to its anti-inflammatory, anti-apoptotic, antioxidant and androgenic nature.


Subject(s)
Microplastics , Testis , Rats , Male , Animals , Microplastics/metabolism , Microplastics/pharmacology , Plastics/metabolism , Polystyrenes/toxicity , Polystyrenes/metabolism , Oxidative Stress , Rats, Wistar , Semen/metabolism , Antioxidants/pharmacology
3.
Lipids Health Dis ; 22(1): 68, 2023 May 27.
Article in English | MEDLINE | ID: mdl-37237272

ABSTRACT

BACKGROUND: The epithelial lining of the gut expresses intestinal fatty-acid binding proteins (I-FABPs), which increase in circulation and in plasma concentration during intestinal damage. From the perspective of obesity, the consumption of a diet rich in fat causes a disruption in the integrity of the gut barrier and an increase in its permeability. HYPOTHESIS: There is an association between the expression of I-FABP in the gut and various metabolic changes induced by a high-fat (HF) diet. METHODS: Wistar albino rats (n = 90) were divided into three groups (n = 30 per group), viz. One control and two HF diet groups (15 and 30%, respectively) were maintained for 6 weeks. Blood samples were thus collected to evaluate the lipid profile, blood glucose level and other biochemical tests. Tissue sampling was conducted to perform fat staining and immunohistochemistry. RESULTS: HF diet-fed rats developed adiposity, insulin resistance, leptin resistance, dyslipidemia, and increased expression of I-FABP in the small intestine compared to the control group. Increased I-FABP expression in the ileal region of the intestine is correlated significantly with higher fat contents in the diet, indicating that higher I-FABP expression occurs due to increased demand of enterocytes to transport lipids, leading to metabolic alterations. CONCLUSION: In summary, there is an association between the expression of I-FABP and HF diet-induced metabolic alterations, indicating that I-FABP can be used as a biomarker for intestinal barrier dysfunction.


Subject(s)
Diet, High-Fat , Obesity , Animals , Rats , Diet, High-Fat/adverse effects , Rats, Wistar , Obesity/genetics , Obesity/metabolism , Biomarkers , Enterocytes/metabolism
4.
Molecules ; 27(10)2022 May 20.
Article in English | MEDLINE | ID: mdl-35630774

ABSTRACT

Honey is the principal premier product of beekeeping familiar to Homo for centuries. In every geological era and culture, evidence can be traced to the potential usefulness of honey in several ailments. With the advent of recent scientific approaches, honey has been proclaimed as a potent complementary and alternative medicine for the management and treatment of several maladies including various neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and multiple sclerosis, etc. In the literature archive, oxidative stress and the deprivation of antioxidants are believed to be the paramount cause of many of these neuropathies. Since different types of honey are abundant with certain antioxidants, primarily in the form of diverse polyphenols, honey is undoubtedly a strong pharmaceutic candidate against multiple neurological diseases. In this review, we have indexed and comprehended the involved mechanisms of various constituent polyphenols including different phenolic acids, flavonoids, and other phytochemicals that manifest multiple antioxidant effects in various neurological disorders. All these mechanistic interpretations of the nutritious components of honey explain and justify the potential recommendation of sweet nectar in ameliorating the burden of neurological disorders that have significantly increased across the world in the last few decades.


Subject(s)
Alzheimer Disease , Honey , Antioxidants/pharmacology , Antioxidants/therapeutic use , Flavonoids , Honey/analysis , Humans , Polyphenols/pharmacology , Polyphenols/therapeutic use
5.
Pak J Med Sci ; 38(1): 84-89, 2022.
Article in English | MEDLINE | ID: mdl-35035405

ABSTRACT

BACKGROUND & OBJECTIVES: Primary Microcephaly (MCPH) is a rare neurogenetic disease, manifesting congenitally reduced head circumference and non-progressive intellectual disability (ID). To date, twenty-eight genes with biallelic mutations have been reported for this disorder. The study aimed for molecular genetic characterization of Pakistani families segregating MCPH. METHODS: We studied two unrelated consanguineous families (family A and B) presenting >2 patients with diagnostic symptoms of MCPH, born to asymptomatic parents. We employed whole-exome sequencing (WES) of probands to find putative causal mutations. The candidate variants were further confirmed and analyzed for co-segregation by Sanger sequencing of all available members of each family. This study was conducted at Government College University, Faisalabad, Pakistan, and Cologne Center for Genomics (CCG), University of Cologne, Germany; during 2017-2020. RESULTS: We identified a novel homozygous variant c.10097_10098delGA, p.(Gly3366Glufs*19) in exon 26 of ASPM gene in family A which presents with moderate intellectual disability, speech impairment, visual abnormalities, seizures, and ptyalism. Family B was found to segregate nonsense, homozygous variant c.448C>T p.(Arg150*) in CDK5RAP2. The patients also exhibited mild to severe seizures without ptyalism that has not been previously reported in patients with mutations in the CDK5RAP2 gene. CONCLUSION: We report a novel mutation in ASPM and ultra-rare mutation in the CDK5RAP2 gene, both causing primary microcephaly. The study expands the mutational spectrum of the ASPM gene to 212, and also adds to the clinical spectrum of CDK5RAP2 mutations. It also demonstrated the utility of WES in the investigation and genetic diagnosis of genetically heterogeneous disorders like MCPH. These findings would aid in diagnostic and preventive strategies including carrier screening, cascade testing, and genetic counselling.

6.
Clin Genet ; 100(4): 486-488, 2021 10.
Article in English | MEDLINE | ID: mdl-34270086

ABSTRACT

Jawad syndrome is a multiple congenital anomaly and intellectual disability syndrome with mutation in RBBP8 reported only in two families. Here, we report on two new families from Pakistan and identified a previously reported variant in RBBP8, NM_002894.3:c.1808-1809delTA. We could show that this mutation impairs splicing resulting in two different abnormal transcripts. Finally, we could verify a shared haplotype among all four families and estimate the founder event to have occurred some 24 generations ago.


Subject(s)
Endodeoxyribonucleases/genetics , Fingers/abnormalities , Founder Effect , Hand Deformities, Congenital/diagnosis , Hand Deformities, Congenital/genetics , Intellectual Disability/diagnosis , Intellectual Disability/genetics , Microcephaly/diagnosis , Microcephaly/genetics , Mutation , RNA Splicing , Toes/abnormalities , Facies , Genetic Association Studies , Genetic Predisposition to Disease , Humans , Pakistan , Pedigree , Phenotype , Sequence Analysis, DNA , Exome Sequencing
7.
Pak J Pharm Sci ; 34(6(Supplementary)): 2309-2315, 2021 Nov.
Article in English | MEDLINE | ID: mdl-35039268

ABSTRACT

The liver is a fundamental metabolic organ that performs many essential functions including the detoxification of toxic substances present in the body. Exposure to various toxicants leads the liver towards hepatic injury. This study was planned to estimate the hepatoprotective and regenerative efficacy of Quinoa seeds (Chenopodium quinoa) extract against carbon tetrachloride (CCl4) induced liver damage. At a dose of 1ml/kg (153.8mg/kg) body weight carbon tetrachloride (CCl4) was used intraperitoneally to induce hepatic injury in Wistar rats. Silymarin (30mg/kg body weight, p.o.), an antioxidant was used as a reference standard drug. Subsequently, ethanolic extract of Quinoa seeds (QEE) was administered at 400 and 600mg/kg body weight through oral gavage. Various biochemical and regenerative biomarkers were assessed to evaluate the potential efficacy of QEE in liver tissue regeneration. Results revealed that QEE administration significantly reduced the CCl4-induced raised quantities of alanine transaminase (ALT), aspartate transaminase (AST), and total oxidative stress (TOS) while, significantly improved the level of triiodothyronine (T3), thyroxine (T4), albumin and total protein concentration in QEE treated groups. The expression level of IGF-1, FOXA-2, Stmn-2, SPP-1 was found significantly down-expressed. It is concluded that QEE treatment has the regenerative and hepatoprotective effect.


Subject(s)
Antioxidants/pharmacology , Chemical and Drug Induced Liver Injury/prevention & control , Chenopodium quinoa , Liver Regeneration/drug effects , Liver/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Seeds , Animals , Antioxidants/isolation & purification , Biomarkers/blood , Carbon Tetrachloride , Cell Proliferation , Chemical and Drug Induced Liver Injury/etiology , Chemical and Drug Induced Liver Injury/metabolism , Chemical and Drug Induced Liver Injury/pathology , Chenopodium quinoa/chemistry , Disease Models, Animal , Liver/metabolism , Liver/pathology , Plant Extracts/isolation & purification , Rats, Wistar , Seeds/chemistry , Silymarin/pharmacology
8.
Pak J Pharm Sci ; 34(4(Supplementary)): 1535-1540, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34799329

ABSTRACT

The present work was conceptualized to determine the potential protective effects of curcumin on arsenic-induced kidney damage in male albino rat model. Thirty six male albino rats were selected, weighed about 175±10g and classified into four groups (9 rats in each group) such as C group (control with basal diet), Cur group (curcumin 200mg/kg body weight), AI group (arsenic-induced 5mg/kg body weight) and AI + Cur group (arsenic 5mg/kg+curcumin 200mg/kg body weight), respectively. Arsenic and curcumin were offered through the gavage method once daily with basal diet. The different analyzed parameters showed that arsenic-induced elevation of aspartate amino transferase, alkaline phosphatase, bilirubin urea, alanine aminotransferase and creatinine significantly decreased with curcumin application in AI + Cur group. Similarly, the statistically significant decline of low-density lipoprotein (LDL), cholesterol, triglyceride and increased in high-density lipoprotein (HDL) was observed in rats of AI + Cur group with curcumin treatment as compared to the rats of AI group. The level of different enzymes of the liver as well as kidney was noted depleted on arsenic exposure whereas increased in level was observed with curcumin application in AI + Cur group. Moreover, pathological histology changes were also recorded. The outcomes suggest that curcumin has a potential effect against arsenic-induced toxicity in biological model.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Arsenic/toxicity , Chemical and Drug Induced Liver Injury/drug therapy , Curcumin/pharmacology , Hyperlipidemias/drug therapy , Kidney Diseases/drug therapy , Animals , Kidney Diseases/chemically induced , Rats
9.
J Transl Med ; 18(1): 349, 2020 09 14.
Article in English | MEDLINE | ID: mdl-32928224

ABSTRACT

BACKGROUND: Omega-3 fatty acids (Ω-3 PUFAs) may help to improve health status in polycystic ovarian syndrome (PCOS) by reducing numerous metabolic disorders (insulin sensitivity, hyperinsulinemia, lipid profile, obesity and inflammation). To evaluate the current objective, 16 weeks (6 weeks of adjustment period followed by 10 weeks of collection period) research trial was planned to check the impact of different sources of Ω-3 PUFAs (synthetic Ω-3, flaxseed and fish oil) on nutrient digestibility, weight gain, productive (lipid profile, glucose and insulin), reproductive profile (progesterone, follicle stimulating hormone (FSH), estrogen, luteinizing hormone (LH) and prolactin) and histological study of ovarian tissues in Wistar female rats. METHODS: Forty-five rats of 130 ± 10 g weight were divided into 5 groups, each having 9 rats: NC (negative control without PCOS), PC (positive control with PCOS), SO (synthetic omega-3 containing ALA, EPA and DHA), FO (flaxseed oil) and F (fish oil) fed at 300 mg/kg/orally/daily of these sources were added in the basal diets while PC and NC received only the basal diet. Food and water were offered ad libitum. PCOS was induced in the rats fed of PC, SO, FO and F diets group by single intramuscular injection of estradiol-valerate (4 mg/rat/IM). Body weight and blood glucose was recorded weekly. At 16th week of trial, blood samples were collected for lipid and hormonal analysis. Ovarian tissues were removed for pathological evaluation. Digestibility was measured by total collection method. RESULTS: Cholesterol, triglycerides and low-density lipoproteins were reduced in SO, FO and F groups when compared with rats of PC group. However, increasing trend of high-density lipoprotein (HDL) was found in same groups. The highest HDL (36.83 ± 0.72 mg/dL) was observed in rats fed F diet. In case of a hormonal profile, testosterone, LH and insulin levels showed a significant reduction after treatments. Blood glucose results showed significantly reducing trend in all the rats fed with Ω-3 PUFAs sources than PC from 5 to 10th week of trial. However, similar trend was noticed in rat's body weight at the end of 6th week. In ovarian morphology, different stages of follicles were observed in groups fed SO, FO and F diets. Nutrient digestibility in PCOS induced rats was remained non-significant. CONCLUSIONS: The three sources of Ω-3 PUFAs had effective role in improving lipid and hormonal profile, reducing blood glucose, weight gain and histopathological damages in PCOS rats. However, fish oil source might be an innovative approach to cure PCOS via reducing the weight and metabolic anomalies due to EPA and DHA.


Subject(s)
Fatty Acids, Omega-3 , Polycystic Ovary Syndrome , Animals , Blood Glucose , Fatty Acids, Omega-3/pharmacology , Female , Humans , Polycystic Ovary Syndrome/drug therapy , Rats , Rats, Wistar , Weight Gain
10.
Crit Rev Food Sci Nutr ; 60(3): 351-374, 2020.
Article in English | MEDLINE | ID: mdl-30614244

ABSTRACT

Brain is a central and pivotal organ of human body containing the highest lipids content next to adipose tissue. It works as a monitor for the whole body and needs an adequate supply of energy to maintain its physiological activities. This high demand of energy in the brain is chiefly maintained by the lipids along with its reservoirs. Thus, the lipid metabolism is also an important for the proper development and function of the brain. Being a prominent part of the brain, lipids play a vast number of physiological activities within the brain starting from the structural development, impulse conduction, insulation, neurogenesis, synaptogenesis, myelin sheath formation and finally to act as the signaling molecules. Interestingly, lipids bilayer also maintains the structural integrity for the physiological functions of protein. Thus, in light to all of these activities, lipids and its metabolism can be attributed pivotal for brain health and its activities. Decisively, the impaired/altered metabolism of lipids and its intermediates puts forward a key step in the progression of different brain ailments including neurodegenerative, neurological and neuropsychiatry disorders. Depending on their associated underlying pathways, they serve as the potential biomarkers of these disorders and are considered as necessary diagnostic tools. The present review discusses the role and level of altered lipids metabolism in brain diseases including neurodegenerative diseases, neurological diseases, and neuropsychiatric diseases. Moreover, the possible mechanisms of altered level of lipids and their metabolites have also been discussed in detail.


Subject(s)
Brain Diseases/metabolism , Lipid Metabolism , Lipids/analysis , Biomarkers/analysis , Biomarkers/metabolism , Brain/metabolism , Brain/pathology , Brain Diseases/pathology , Humans
11.
Pak J Pharm Sci ; 33(6(Supplementary)): 2801-2807, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33879440

ABSTRACT

Peripheral nerve injuries result in sensorimotor functional loss, leading to permanent disability and physical dependency with immense cost and reduced quality of life. These injuries are among those complicated medical situations which still are waiting for their first-line treatment. This study was designed to investigate the role of Calotropis procera (crude roots) in accelerating functional retrieval following mechanically induced sciatic nerve injury in healthy albino male mice. Following acclimatization, mice were grouped equally as "Control" fed on normal chow and "Root" fed on C. procera root (100mg/kg/day) mixed chow. A mechanical crush was induced in right sciatic nerve of animals. Behavioral analyses (grip strength, SFI, pinprick and hot plate tests) were conducted for assessing sensorimotor function reclamation and blood was collected for oxidative stress assessment. Significantly earlier retrieval of sensorimotor activities (p<0.05), reduced total oxidant status, increased total antioxidant capacity with prominently enhanced arylesterase and paraoxonase activities (p<0.001) in treatment group suggested positive impact of C. procera roots on quickening functional recovery and combating oxidative stress following nerve injury. Thus C. procera root can be considered as potential candidate drug for further investigation to seek bioactive compound/s that may actually responsible for ameliorative functional recovery following nerve injury.


Subject(s)
Calotropis , Oxidative Stress/drug effects , Peripheral Nerve Injuries/drug therapy , Animals , Disease Models, Animal , Male , Mice , Motor Activity/drug effects , Peripheral Nerve Injuries/physiopathology , Peripheral Nerve Injuries/rehabilitation , Phytotherapy , Plant Roots , Recovery of Function
12.
Lipids Health Dis ; 18(1): 26, 2019 Jan 25.
Article in English | MEDLINE | ID: mdl-30683111

ABSTRACT

Brain is a vital organ of the human body which performs very important functions such as analysis, processing, coordination, and execution of electrical signals. For this purpose, it depends on a complex network of nerves which are ensheathed in lipids tailored myelin; an abundant source of lipids in the body. The nervous system is enriched with important classes of lipids; sphingolipids and cholesterol which compose the major portion of the brain particularly in the form of myelin. Both cholesterol and sphingolipids are embedded in the microdomains of membrane rafts and are functional units of the neuronal cell membrane. These molecules serve as the signaling molecules; hold important roles in the neuronal differentiation, synaptogenesis, and many others. Thus, their adequate provision and active metabolism are of crucial importance in the maintenance of physiological functions of brain and body of an individual. In the present review, we have highlighted the physiological roles of cholesterol and sphingolipids in the development of the nervous system as well as the association of their altered metabolism to neurological and neurodegenerative diseases.


Subject(s)
Brain/growth & development , Cholesterol/metabolism , Nervous System Diseases/genetics , Sphingolipids/metabolism , Animals , Brain/metabolism , Cell Membrane/genetics , Cholesterol/genetics , Humans , Lipids/genetics , Membrane Microdomains/genetics , Myelin Sheath/genetics , Myelin Sheath/metabolism , Nervous System Diseases/metabolism , Nervous System Diseases/physiopathology , Neurons/metabolism , Neurons/pathology , Sphingolipids/genetics
13.
Molecules ; 24(12)2019 Jun 13.
Article in English | MEDLINE | ID: mdl-31200495

ABSTRACT

Neurodegenerative and neuropsychiatric diseases are characterized by the structural and functional abnormalities of neurons in certain regions of the brain. These abnormalities, which can result in progressive neuronal degeneration and functional disability, are incurable to date. Although comprehensive efforts have been made to figure out effective therapies against these diseases, partial success has been achieved and complete functional recovery is still not a reality. At present, plants and plant-derived compounds are getting more attention because of a plethora of pharmacological properties, and they are proving to be a better and safer target as therapeutic interventions. This review aims to highlight the roles of tannins, 'the polyphenol phytochemicals', in tackling neurodegenerative diseases including Alzheimer's and Parkinson's diseases as well as neuropsychiatric disorders like depression. Among the multifarious pharmacological properties of tannins, anti-oxidative, anti-inflammatory, and anti-cholinesterase activities are emphasized more in terms of neuroprotection. The current review also throws light on mechanistic pathways by which various classes of tannins execute neuroprotective effects. Despite their beneficial properties, some harmful effects of tannins have also been elaborated.


Subject(s)
Neuroprotective Agents/chemistry , Neuroprotective Agents/therapeutic use , Tannins/chemistry , Tannins/therapeutic use , Alzheimer Disease/drug therapy , Humans , Neuropsychiatry , Parkinson Disease/drug therapy , Phytochemicals/chemistry , Phytochemicals/therapeutic use
14.
Pak J Pharm Sci ; 32(5(Supplementary)): 2245-2250, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31894050

ABSTRACT

The aim of the present study was to purify, hydrolyze and modify the Cordia myxa gum to document its binder potential in pharmaceutical tablets formulation. The hydrolysis and modification was carried out to remove impurities, roughness, increase thermal stability and to improve the functional properties of biopolymers. Physiochemical properties such as pH, solubility, viscosity, swelling index, bulk and tapped density was performed prior to investigate binder potential. The binder potential of Cordia myxa gum was studied in its different forms such as crude, purified, modified and hydrolyzed in paracetamol tablets and was compared with standard hydroxypropyl methylcellulose (HPMC) being used as synthetic binder. Tablets were prepared by direct compression method and evaluated for weight uniformity, hardness, friability, disintegration time and dissolution analysis. Prepared tablets with selected gums exhibit faster and slower dissolution profile in the same dissolution system. The crude gum has high dissolution rate whereas the hydrolyzed and modified gums showed less dissolution rate. The hydrolyzed and modified gums having faster release rate and it could be helpful in conventional tablet formulations efficiently as compared to synthetic HPMC binder.


Subject(s)
Cordia/chemistry , Dietary Supplements , Plant Gums/isolation & purification , Tablets/chemistry , Drug Compounding , Plant Gums/chemistry , Solubility
15.
Pak J Pharm Sci ; 32(2 (Supplementary)): 751-757, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31103967

ABSTRACT

Gut microbiome, a new organ; represent targets to alter pharmacokinetics of orally administered drugs. Recently, in vitro trials endorsed the idea that orally administered drugs interact and some of their quantity may be taken up by normal microbiome during transit through gut. Such transport mechanisms in microbiome may compete for drug with the host itself. Currently, no data confirms specific transport system for paracetamol uptake by gut microbiome. In vivo trial was conducted in normal healthy male rats (n=36). Paracetamol was administered orally in a single dose of 75mg/kg to isolate microbial mass after transit of 2, 3, 4, 5 and 6 hours post drug administration. Paracetamol absorbance by microbiome was pursued by injecting extracted microbial lysate in RP-HPLC-UV with C18 column under isocratic conditions at 207nm using acetonitrile and water (25:75 v/v) pH 2.50 as mobile phase. Paracetamol absorbance (14.10±0.75µg/mg of microbial mass) and percent dose recovery (13.16±0.55%) seen at transit of 4 hours was significantly higher (P<0.05) compared to other groups. Study confirms the hypothesis of homology between membrane transporters of the gut microbiome and intestinal epithelium. Orally administered drugs can be absorbed by gut microbes competitively during transit in small intestine and it varies at various transit times.


Subject(s)
Acetaminophen/pharmacokinetics , Gastrointestinal Microbiome/physiology , Acetaminophen/administration & dosage , Acetaminophen/analysis , Administration, Oral , Animals , Chromatography, High Pressure Liquid , Gastrointestinal Microbiome/drug effects , Intestinal Absorption , Intestine, Small/drug effects , Intestine, Small/physiology , Male , Rats
16.
Pak J Pharm Sci ; 32(2 (Supplementary)): 785-792, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31103973

ABSTRACT

Peripheral nerve injury is a common condition with a multitude of signs and symptoms. The major consequence of injury is limited physical activity. Presently, we are lacking effective therapies for PNI and it is need of the hour is to explore potential remedies for the recovery of functional loss. Here, we have investigated the role of crude Cannabis sativa L. leaf powder in promoting functions recovery, in mouse model subjected to a traumatic sciatic nerve injury. A dose of 200mg/kg of the body weight per day was administered orally from the day of nerve crush till the end of the experiment. The motor functions were evaluated by measuring sciatic functional index, muscle grip strength and muscle mass; whereas the sensory functions were assessed by hotplate test. The haematology and serum analyses were carried out to estimate the effect of treatment on the systemic index and oxidative stress. The gain of motor functions was significantly improved and was early noticed in the treated mice. Restoration of muscle mass and elevated haemoglobin level were statistically significant in the treatment group. This study indicates that Cannabis sativa L. supplementation accelerates the motor functions recovery after nerve compression injury.


Subject(s)
Cannabis , Peripheral Nerve Injuries/drug therapy , Sciatic Nerve/injuries , Animals , Blood Glucose/metabolism , Body Weight/drug effects , Dietary Supplements , Disease Models, Animal , Eating/drug effects , Hemoglobins/metabolism , Male , Mice , Motor Activity/drug effects , Oxidative Stress/drug effects , Peripheral Nerve Injuries/blood , Peripheral Nerve Injuries/physiopathology , Plant Leaves/chemistry , Powders/pharmacology , Recovery of Function
17.
Pak J Pharm Sci ; 32(4(Supplementary)): 1761-1766, 2019 Jul.
Article in English | MEDLINE | ID: mdl-31680070

ABSTRACT

Peripheral nerve injury is a complex condition which results in restricted physical activity. Despite the tremendous efforts to figure out effective remedies, the complete functional retrieval is still a goal to be achieved. So, the need of hour is the exploration of potential natural compounds to recover this functional loss. Here, we have investigated the role of a local plant "Neurada procumbens" in ameliorating the functional recovery after an induced nerve compression injury in a mouse model. A dose of N. procumbens (50mg/kg of body weight) was administered orally from the day of injury to onwards. The motor functional recovery was assessed by evaluating muscle grip strength and sciatic functional index; while the sensory functions were gauged by the hotplate test. The serological parameters were carried out to analyze the effect of N. procumbens on oxidative stress level. The recovery of sensory and motor functions was significantly improved and perceived earlier in the treatment group. Moreover, the elevated antioxidant level was statistically significant in the treatment group. These results indicate that the supplementation of N. procumbens accelerates functional recovery after sciatic nerve crush injury.


Subject(s)
Peripheral Nerve Injuries/drug therapy , Plant Preparations/pharmacology , Recovery of Function/drug effects , Sciatic Nerve/drug effects , Sciatic Neuropathy/drug therapy , Animals , Antioxidants/pharmacology , Disease Models, Animal , Mice , Motor Activity/drug effects , Nerve Regeneration/drug effects , Oxidative Stress/drug effects
18.
Molecules ; 23(4)2018 Apr 02.
Article in English | MEDLINE | ID: mdl-29614843

ABSTRACT

Neurodegeneration is a progressive loss of neuronal cells in certain regions of the brain. Most of the neurodegenerative disorders (NDDs) share the communal characteristic such as damage or reduction of various cell types typically including astrocytes and microglial activity. Several compounds are being trialed to treat NDDs but they possess solitary symptomatic advantages along with copious side effects. The finding of more enthralling and captivating compounds to suspend and standstill the pathology of NDDs will be considered as a hallmark of present times. Phytochemicals possess the potential to alternate the synthetic line of therapy against NDDs. The present review explores the potential efficacy of plant-derived flavonoids against most common NDDs including Alzheimer's disease (AD) and Parkinson's disease (PD). Flavonoids are biologically active phytochemicals which possess potential pharmacological effects, including antiviral, anti-allergic, antiplatelet, anti-inflammatory, anti-tumor, anti-apoptotic and anti-oxidant effects and are able to attenuate the pathology of various NDDs through down-regulating the nitric oxide (NO) production, by reducing the tumor necrosis factor-α (TNF-α), by reducing the excitotoxicity of superoxide as well as acting as tyrosine kinase (TK) and monoamine oxidase (MAO) inhibiting enzyme.


Subject(s)
Alzheimer Disease/drug therapy , Flavonoids/therapeutic use , Parkinson Disease/drug therapy , Alzheimer Disease/metabolism , Animals , Antioxidants/therapeutic use , Humans , Monoamine Oxidase/metabolism , Parkinson Disease/metabolism , Tumor Necrosis Factor-alpha/metabolism
19.
Pak J Pharm Sci ; 31(4(Supplementary)): 1565-1570, 2018 Jul.
Article in English | MEDLINE | ID: mdl-30058549

ABSTRACT

Prevalence of hepatitis C virus (HCV) has been seen in more than 15% of Pakistani population. For the treatment of this infection, only two medicines, interferon, and ribavirin were approved in 1998. The concerned physicians evaluate side effects of these two antiviral drugs only during the treatment period. The long-term extra hepatic side effects are being neglected. This retrospective study was conducted with reference to induced infertility in HCV treated 40 male patients from the period 2008-2015. Possible effects of interferon therapy on fertility hormones and seminal parameters were assessed. Level of fertility hormones like serum Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), and testosterone was measured. For seminal parameters, guidelines from World Health Organization (WHO) were followed. Among forty cases of HCV patients who received interferon, only 14 (35%) have children and 26 (65%) could not conceive (p = 0.0372). After HCV treatment, HCV positive patients showed a significant change in the level of FSH, LH (p<0.05). Especially, it decreased testosterone level (p=0.0096). Similarly, HCV treatment significantly decreased sperm count (p=0.001) and motility (p=0.0005).


Subject(s)
Antiviral Agents/adverse effects , Infertility, Male/blood , Infertility, Male/chemically induced , Interferons/adverse effects , Sperm Motility/drug effects , Adult , Follicle Stimulating Hormone/antagonists & inhibitors , Follicle Stimulating Hormone/blood , Hepatitis C/blood , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Humans , Infertility, Male/diagnosis , Luteinizing Hormone/antagonists & inhibitors , Luteinizing Hormone/blood , Male , Middle Aged , Sperm Motility/physiology , Testosterone/antagonists & inhibitors , Testosterone/blood , Young Adult
20.
Pak J Pharm Sci ; 31(5(Supplementary)): 2163-2168, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30393228

ABSTRACT

Mushrooms, a treasure of diverse bioactive scaffolds, have been widely admired due to their nutritional and medicinal significance all over the world. The current study intended to evaluate the therapeutic potentiality of an edible mushroom, Leucoagaricus leucothites (Vittad.) Wasser. Thus, anti-oxidant potential of L. leucothites was determined using DPPH assay and for the determination of anti-microbial potential agar dilution procedure was followed. TOS (total oxidant status), TAS (total anti-oxidant status), and OSI (oxidative stress index) values were evaluated utilizing Rel Assay Kits. For the assessment of heavy metal contents, wet decomposition approach with atomic absorption spectrophotometry was adopted. Screening of phytochemicals present in ethanolic extract of L. leucothites were determined by HPLC. TAS, TOS and OSI values were found to be 8.291mmol/L, 10.797µmol/L and 0.130 respectively. Our results declared that heavy metal contents are generally in the safe range. Phytochemical analysis of L. leucothites has affirmed the presence of important phenolics such as gallic acid, catechin, and hesperidin. Investigations on anti-oxidant and anti-microbial potential of L. leucothites has uncovered the fact that this naturally occurring, biologically active, and therapeutically effective mushroom specie has natural borne anti-oxidant and anti-microbial potential and it would be worthwhile to use it for nutritional as well as medicinal purpose.


Subject(s)
Agaricales , Anti-Infective Agents/pharmacology , Antioxidants/pharmacology , Metals, Heavy , Oxidative Stress/drug effects , Agaricales/chemistry , Anti-Infective Agents/isolation & purification , Antioxidants/isolation & purification , Candida albicans/drug effects , Candida albicans/growth & development , Escherichia coli/drug effects , Escherichia coli/physiology , Humans , Metals, Heavy/isolation & purification , Oxidative Stress/physiology
SELECTION OF CITATIONS
SEARCH DETAIL