Therapeutic potential of salvigenin to combat atrazine induced liver toxicity in rats via regulating Nrf-2/Keap-1 and NF-κB pathway.

Atrazine (ATR) is the second most extensively used herbicide which adversely affects the body organs including liver. Salvigenin (SGN) is a flavonoid which demonstrates a wide range of biological and pharmacological abilities. This study was planned to assess the protective ability of SGN to avert ATR induced liver damage in rats. Thirty-two rats (Rattus norvegicus) were divided into four groups including control, ATR (5 mg/kg), ATR (5 mg/kg) + SGN (10 mg/kg) and SGN (10 mg/kg) alone supplemented group. ATR exposure reduced the expression of Nrf-2 while instigating an upregulation in Keap-1 expression. Furthermore, the activities of catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD), heme­oxygenase-1 (HO-1) and glutathione reductase (GSR) contents were decreased while increasing reactive oxygen species (ROS) and malondialdehyde (MDA) levels after ATR treatment. Moreover, ATR poisoning increased the levels of ALT, AST, and ALP while reducing the levels of total proteins, and albumin in hepatic tissues of rats. Besides, ATR administration escalated the expressions of Bax and Caspase-3 while inducing a downregulation in the expressions of Bcl-2. Similarly, ATR intoxication increased the levels of Interleukin-6 (IL-6), Nuclear factor kappa-B (NF-κB), Interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and the activity of cyclooxygenase-2 (COX-2). Furthermore, ATR disrupted the normal histology of hepatic tissues. However, SGN treatment remarkably protected the liver tissues via regulating antioxidant, anti, inflammatory, anti-apoptotic as well as histology parameters. Therefore, it is concluded that SGN can be used as therapeutic agent to combat ATR-induced hepatotoxicity.

Mechanisms of medicinal, pharmaceutical, and immunomodulatory action of probiotics bacteria and their secondary metabolites against disease management: an overview.

Probiotics or bacteriotherapy is today's hot issue for public entities (Food and Agriculture Organization, and World Health Organization) as well as health and food industries since Metchnikoff and his colleagues hypothesized the correlation between probiotic consumption and human's health. They contribute to the newest and highly efficient arena of promising biotherapeutics. These are usually attractive in biomedical applications such as gut-related diseases like irritable bowel disease, diarrhea, gastrointestinal disorders, fungal infections, various allergies, parasitic and bacterial infections, viral diseases, and intestinal inflammation, and are also worth immunomodulation. The useful impact of probiotics is not limited to gut-related diseases alone. Still, these have proven benefits in various acute and chronic infectious diseases, like cancer, human immunodeficiency virus (HIV) diseases, and high serum cholesterol. Recently, different researchers have paid special attention to investigating biomedical applications of probiotics, but consolidated data regarding bacteriotherapy with a detailed mechanistically applied approach is scarce and controversial. The present article reviews the bio-interface of probiotic strains, mainly (i) why the demand for probiotics?, (ii) the current status of probiotics, (iii) an alternative to antibiotics, (iv) the potential applications towards disease management, (v) probiotics and industrialization, and (vi) futuristic approach.

Black coffee mitigates diethyl phthalate disrupted folliculogenesis, reduced gonadotropins, and ovarian lesions in female albino mice.

Phthalates are multifunctional compounds with extensive applications and emerging environmental pollutants. Due to their ubiquity in the environment and unavoidable exposure to humans, concerns have been voiced about public health dangers. This study was aimed to explore the diethyl phthalate (DEP) toxicity and the potential protective effect of black coffee in female Swiss albino mice. Four-week-old mice, weighing 12 ± 1 g were segregated into five groups (n = 10), designated as G-I (without any treatment), G-II (treated with corn oil), G-III (exposed to 1.5 mg/g body wt. (B.W.) DEP), G-IV (received 2 µg/g B.W coffee), and G-V (co-administrated with 1.5 mg/g DEP and 2 µg/g B.W coffee). Before dose administration, the coffee extract was assessed for its antioxidant potential through FRAP, TPC, and GC-MS analyses. Respective phthalates/coffee doses were administrated orally, once a day for 8 weeks consecutively starting from the prepubescent stage. After 56 days, mice were acclimated for 4 days then dissected. Morphological assessments showed an irregular shape of the ovaries in DEP-treated mice as compared to the control. The average bodyweight of DEP-intoxicated mice (p ≤ 0.05) increased notably against control, while DEP plus coffee group showed a regular gain in the average weight of mice. The gonado-somatic index showed non-significant variations among all groups. Micrometric studies showed that the diameter of secondary follicles (115 µm) in the ovaries of DEP-exposed mice (p ≤ 0.001) decreased significantly as compared to control (204 µm); conversely, follicular diameter in the coffee control group (248) increased significantly. Serum FSH and LH levels were significantly increased in DEP-exposed mice with a noteworthy decrease in estrogen level while hormonal levels of all other groups were comparable to control. Histological sections of DEP-exposed mice ovaries showed anatomical disruptions contrary to other groups, which were comparable with control. Antioxidant potential was checked in ovaries homogenates; FRAP values showed a notable decrease in DEP group in comparison with the control group, in contrast to G-V, when DEP was co-administrated with coffee. This study concluded that black coffee has protective effect, against DEP-instigated reproductive toxicity in Swiss albino female mice.

Vitamin K: A novel cancer chemosensitizer.

Cancer incidences are growing rapidly and causing millions of deaths globally. Cancer treatment is one of the most exigent challenges. Drug resistance is a natural phenomenon and is considered one of the major obstacles in the successful treatment of cancer by chemotherapy. Combination therapy by the amalgamation of various anticancer drugs has suggested modulating tumor response by targeting various signaling pathways in a synergistic or additive manner. Vitamin K is an essential nutrient and has recently been investigated as a potential anticancer agent. The combination of vitamin K analogs, such as vitamins K1, K2, K3, and K5, with other chemotherapeutic drugs have demonstrated a safe, cost-effective, and most efficient way to overcome drug resistance and improved the outcomes of prevailing chemotherapy. Published reports have shown that vitamin K in combination therapy improved the efficacy of clinical drugs by promoting apoptosis and cell cycle arrest and overcoming drug resistance by inhibiting P-glycoprotein. In this review, we discuss the mechanism, cellular targets, and possible ways to develop vitamin K subtypes into effective cancer chemosensitizers. Finally, this review will provide a scientific basis for exploiting vitamin K as a potential agent to improve the efficacy of chemotherapeutic drugs.

Evaluation of sex steroid hormones and reproductive irregularities in diethyl phthalate-exposed premature mice: modulatory effect of raw honey against potential anomalies.

Phthalates, plasticizing chemicals, are top-rated environmental contaminants. Diethyl phthalate (DEP), a chief member of this family, was declared a potent endocrine disruptor and carcinogen in animals and humans. The current study was designed to explore the probable reproductive damage induced by DEP and the therapeutic efficacy of raw honey in male albino mice. Four-week-old 50 male mice were randomized equally in five groups, as control (C) received 0.1 ml distilled water; vehicle control (VC) received corn oil (0.1 ml/mouse); DEP (3mg/g/BW) dissolved in corn oil; honey control (HC) administered with honey (0.2 mg/g/day); and phthalate plus honey (P+H) administered with DEP and honey (3mg and 0.2 mg/g/BW/day respectively). Mice were treated through oral gavage for 54 days routinely, acclimatized for 6 days, and dissected. In the first instance, the antioxidant potential and total phenolic contents (TPC) of honey were analyzed through ferric reducing antioxidant power (FRAP) assay and Folin-Ciocalteu assay to confirm the antioxidant capacity of honey. The morphological, morphometric, histological, micrometric, sperm count, and hormonal analyses, and antioxidant capacity test in tissue homogenates were conducted by using tissues (testis, epididymis) and blood samples of mice. Mice exposed to DEP have a significant increase in body weight, LH level, and seminiferous tubule lumen diameter and decrease in the gonado-somatic index, testosterone level, sperm count, and seminiferous tubule diameter. Additionally, histopathology of testes showed interstitial space dilations, exfoliations, Leydig cell atrophy, germ cell degenerations, and spermatid retention in DEP-exposed testes sections. However, concomitant use of honey and DEP had shown a significant improvement in histopathological lesions, steroid hormone levels, and healthy sperm count. By these results, it is concluded that honey possessed antioxidant potential that can efficiently protect DEP-induced anomalies in male mice.

Evaluation of Cadmium Chloride-Induced Toxicity in Chicks Via Hematological, Biochemical Parameters, and Cadmium Level in Tissues.

Cadmium is a heavy metal and a non-biodegradable environmental contaminant, and its omnipresence ensures its recurrent exposure to humans and animals. Its intake by chicks leads to fatal implications. Cadmium chloride (CdCl2) because of its bio-accumulative nature is an emerging threat to the poultry industry as well as to the humans which consumes these cadmium-intoxicated chickens. In the current study, the target was to elucidate the toxic effects of CdCl2on body weight, hematological, and biochemical parameters as well as its bioaccumulation in different organs of broiler chicks. Various concentrations of CdCl2 (0, 12, 24, 38, and 48 mg/kg body weight) were administered orally to five groups (A, B, C, D, and E) of broiler chicks, respectively. The biometric screening of the exposed birds was carried out by hematological parameters such as packed cell volume (PCV), total erythrocyte count (TEC), mean corpuscular hemoglobin concentration (MCHC), total protein, white blood cells (WBC), and hemoglobin (Hb), as well as biochemical parameters superoxide dismutase (SOD), low-density lipoprotein (LDL), glutathione peroxidase (GPx), and high-density lipoprotein (HDL) with commercially available kits. Metal accumulation in different organs was detected using atomic absorption spectrophotometer. The compound exposure produced a varied impact on broiler birds. Hematological parameters showed a significant decrease except for WBC. Biochemical parameters also decreased significantly in a dose-dependent manner. However, it was revealed that the body weight of chickens was not affected considerably after CdCl2 exposure. A direct relationship was detected between the accumulation of metal within tissues (lungs, heart, and flesh) and exposure frequency. It can be deduced that an increase in Cd deposition in tissues may lead to an alteration in hematological-biochemical markers which may significantly contribute to systemic toxicity in broilers.

Multienzyme and Antibacterial Potential of Bacteria Isolated from gut of Asian Honey Bee (Apis cerana Indica), Lahore Using Culture Dependent Method

Abstract The bacteria residing in the gut of honey bees (HB) has demonstrated a significant role in protecting bees against various pathogens, production of honey and wax. However, no information exists about the antibacterial potential of bacterial isolates from gut of Asian HB, Apis cerana Indica F. (Hymenoptera: Apidae), against human pathogens. This study aims to investigate the antibacterial and multienzyme potential of aerobic bacteria from A. cerana gut using culture dependent approach. A total of 12 HB gut bacteria were characterized morphologically and biochemically. These strains were further screened for their antimicrobial activity against pathogenic human microorganisms Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumonia, Bacillus licheniformis and Bacillus subtilis using cross streak (primary screening) and agar well diffusion methods (secondary screening). Preliminary characterization of cell-free supernatant (CFS) of two promising isolates was performed by measuring lactic acid concentrations, enzymatic digestion of antimicrobial compounds, stability over a range of temperature, pH and amplification of spaS (subtilin) and spoA (subtilosin) genes. In primary screening, among 12 HB isolates, eight strains showed statistically significant highest zones of inhibition (p≤0.05) against E. coli, K. pneumoniae and P. aeruginosa. 16S rRNA sequencing revealed that these isolates belong to Bacillus genus, identified as B. tequilensis, B. pumilus, B. xiamenensis, B. subtilis, B. amyloliquefaciens, B. safensis, B. licheniformis, B. altitudinis (Accession numbers: MT186230-MT186237). Secondary screening revealed that among eight isolates, B. subtilis and B. amyloliquefaciens showed statistically significantly strong inhibition (p≤0.05) against all tested pathogens. Antibiotic susceptibility testing revealed that both isolates were resistant to antibiotics and possesses proteolytic, lipolytic and cellulolytic activities. The nature of the compound causing inhibitory activity was found to be proteinaceous and showed stability over a wide range of temperature as well as pH. PCR study confirmed the presence of bacteriocins by successful amplification of important antimicrobial peptide biosynthesis genes spaS and spoA. These results suggest that the HB gut is a home to bacteria that possess antimicrobial activity and important enzymes with antimicrobial potential. To our knowledge, this is the first report demonstrating the antimicrobial potential of bacteria isolated from gut of HB (A. cerana) against human pathogens.

A Study Of Agreement Between Visual Inspection With Acetic Acid Of Cervix And Pap Smear For Cervical Cancer Screening.

BACKGROUND: One of the common causes of mortality and morbidity among young women is cervical cancer. Following a wash of cervix through acetic acid, the Papanicolaou (PAP) smears and the visual inspection with acetic acid (VIA), are compared. Objective of the study was to check the level of agreement between the PAP smear for cancer of cervix and VIA. METHODS: It is a cross-sectional study and was carried out in Obstetrics and Gynaecology department, Sheikh Zaid Hospital, Lahore, Pakistan. All patients were put in lithotomy position and vaginal speculum was applied and pap smear taken followed by 5% acetic acid application to cervix and changes in the cervix noted down. RESULTS: Patients with mean age 48±7.795 years were included. In 30 (12%) and 61 (24.4%) patients diagnosis of cervical cancer was positive on PAP smear and VIA respectively. The agreement between two test was significant with Kappa value = 0.322 and p-value ≤ 0.00. CONCLUSION: Our study revealed that agreement of PAP smear is almost 80%. VIA on the other hand can be used when there is no access to PAP smear.