Cigarettes and other tobacco products are used to obtain nicotine that is responsible for their stimulating effects. However, a lot of other organic and inorganic chemicals are also released along ...with nicotine. Cadmium (Cd) is one of the several heavy metals that are health hazards and is one of the inorganic elements released in tobacco smoke. The in-vitro investigation focused on exploring the effects of nicotine hydrogen tartrate (NHT) and cadmium (Cd) and their toxic interactions in the A549 cell line. In cell viability assay NHT exhibited its IC50 at 11.71 mM concentration, and the IC50 of Cd was found to be 83 µM after a 24 h exposure. Toxic effects of NHT (5 mM and 10 mM), Cd (50 µM and 100 µM), and their combination were also investigated by flowcytometry. The investigation included apoptotic and necrotic events, the effect on different cell cycle phases, and generation of reactive oxygen species by NHT, Cd, and their combination of different concentrations. Data reveal evident toxic effects of NHT, Cd, and NHT + Cd. It also indicates that the toxic interaction of NHT and Cd is not additive and appears to be minimal when compared with NHT or Cd exposures alone.
Methoxy poly(ethylene oxide)-block-poly(ɛ-caprolactone) (PEO-b-PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of ...this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.
Luteolin (LT) is a natural polyphenol water-insoluble compound. LT-loaded nanovesicles (NVs) were prepared by using the solvent evaporation method. LT-NVs were prepared using cholesterol, ...phosphatidylcholine, span 60, and labrasol in a different composition. The prepared LT-NVs were evaluated for encapsulation efficiency, in vitro drug release, and permeation study. The optimized LT-NVs were further evaluated for antioxidant activity and cytotoxicity using the lung cancer cell line. LT-NVs showed nanometric size (less than 300 nm), an optimum polydispersibility index (less than 0.5), and a negative zeta potential value. The formulations also showed significant variability in the encapsulation efficiency (69.44 ± 0.52 to 83.75 ± 0.35%) depending upon the formulation composition. The in vitro and permeation study results revealed enhanced drug release as well as permeation profile. The formulation LT-NVs (F2) showed the maximum drug release of 88.28 ± 1.13%, while pure LT showed only 20.1 ± 1.21% in 12 h. The release data revealed significant variation (p < 0.001) in the release pattern. The permeation results also depicted significant (p < 0.001) enhancement in the permeation across the membrane. The enhanced permeation from LT-NVs was achieved due to the enhanced solubility of LT in the presence of the surfactant. The antioxidant activity results proved that LT-NVs showed greater activity compared to pure LT. The cytotoxicity study showed lesser IC50 value from LT-NVs than the pure LT. Thus, it can be concluded that LT-NVs are a natural alternative to the synthetic drug in the treatment of lung cancer.
The present research has demonstrated the impact of treatment with piperine on hepatic fibrosis induced by the administration of carbon tetrachloride.
In order to study the outcome of piperine ...treatment on hepatic fibrosis caused by carbon tetrachloride administration in male Wistar rats, a total of 24 rats were collected and randomly classified into 4 separate groups each consisting of 6 animals. Group I was assigned as a controlgroup and treated with olive oil for 4 weeks (1 ml/kg, i.p.) with two doses each week. Group II was designated as a toxic group and treated with carbon tetrachloride for 4 weeks (1 ml/kg, 1:1 combination with olive oil, i.p.) with two hepatic fibrosis induction doses each week. Group III was graded as a group I therapy and co-treated with carbon tetrachloride (1 ml/kg, 1:1 combination with olive oil, i.p.) for 4 weeks with two hepatic fibrosis induction doses a week and with piperine (25 mg/kg) for 4 weeks. Group IV was designated as group II therapy and co-treated with carbon tetrachloride (1 ml/kg, 1:1 combination of olive oil, i.p.) for 4 weeks with two hepatic fibrosis induction doses a week and piperine (50 mg/kg) for 4 weeks.
Piperine significantly reduced the carbon tetrachloride augmented activities of liver enzymes, lipid peroxidation, glutathione, hydroxyproline, nitrite, and carbonyl levels. Carbon tetrachloride enhanced Total cholesterol (TC), Triglyceride (TG), Low density lipoprotein (LDL), and Very low density lipoprotein (VLDL) levels, and decreased High density lipoprotein (HDL) level was restored to normal with piperine treatment. Moreover, piperine inhibited the over-expression of pro-inflammatory biomarkers and α-SMA.
The data of the current study demonstrated piperine as a potent hepato-protective agent and recommends the use of piperine for preventing hepatic fibrosis.
Pulicaria arabica has been traditionally utilized in folk medicine for various purposes such as ulcer treatments as well as antidiarrheal agent. Herein, the chemical profiles of Pulicaria arabica ...essential oils (PAEOs) and the in vitro antiproliferative effect of PAEOs were investigated. Hydrodistillation was employed to prepare PAEOs which were then characterized by GC/MS, while the antiproliferative effects were investigated by MTT assay as well as flow cytometric and RT-PCR analysis. Sixty-four (99.99 %) constituents were recognized from PAEOs. Carvotanacetone (36.97 %), (-)-carvomenthone (27.20 %) and benzene, 2-(1,1-dimethylethyl)-1,4-dimethoxy- (6.92 %) were the main components. PAEOs displayed IC50 values ranging from 30 to 50 μg/mL. DNA content analysis revealed that A549 cells exposed to PAEOs exhibited an increase in G1 cells population. The flow cytometry analysis results also showed that the PAEOs antiproliferative effect was mediated via apoptosis induction. Furthermore, a modulation in the pro-apoptotic markers (caspase-3 and Bax) and anti-apoptotic (Bcl-2) was also observed. In conclusion, PAEOs exhibited a moderate anti-proliferative effect on A549 cells through modulating the cell cycle progression and apoptosis initiation. These findings could offer a potential therapeutic use of PAEOs in lung cancer treatment.
•Tuberculosis (TB) treatment regimens can have serious adverse drug reactions that require monitoring.•This report describes adverse drug reactions associated with Directly Observed Treatment ...Strategy (DOTS) protocols.•We define some mechanisms underlying the adverse drug reactions observed following DOTS.•Although males are more likely to have TB, gender did not affect the development of adverse drug reactions.•Although DOTS therapy does require monitoring, it is a highly effective treatment for tuberculosis.
Understanding the appearance of anti-tubercular drug-related adverse drug reactions (ADRs) in patients receiving tuberculosis (TB) treatment is important, and may be related to morbidity and mortality if not recognized early. Here, we aimed to characterize the mechanisms underlying adverse drug reactions due to combination anti-tuberculosis therapy of the Revised National Tuberculosis Control Program (RNTCP).
This was a prospective observational study conducted in 9 DOTS centers of New Delhi, India. All enrolled TB patients receiving first-line tuberculosis treatment as per RNTCP guidelines were monitored for ADRs. All ADRs that appeared during the treatment were recorded and analyzed.
The study included 1011 TB patients on anti-TB treatment under DOTS. According to Naranjo’s probability scale, of a total 351 (34.72%) reported adverse events, 102 (10.09%) were definite, 59 (5.83%) probable, 123 (12.17%) possible, and 67 (6.63%) doubtful. On the Hartwig severity scale, of the 351 adverse drug events, 225 (22.26%) were mild, 105 (10.38%) were moderate, and 21 (2.08%) were severe. Out of 102 reported adverse drug reactions, 81 (79.41%) were moderate and 21 (20.59%), while 65.28% did not experience any ADRs.
Directly Observed Treatment (DOT) is effective and safe compared to daily treatment regimens. Patients receiving DOTS therapy needed close monitoring for adverse events. Therefore, a pharmacovigilance program should be added at the National level to accesses the adverse event incidence.
•Monitoring of liver function tests is very important in patient receiving DOT therapy.•There was no significance difference reported in the differential leucocytes count.•We define mechanisms ...underlying the adverse drug reactions observed following DOTS.•The plasma INH concentration was reported to be high in slow acetylation.•Plasma INH concentration greater than the antimode are slow acetylator.
Isoniazid is the most commonly used drug for treatment of tuberculosis, and is administered individually or in combination with other drugs as standard first line therapy. Offsetting its efficacy, severe adverse effects, especially peripheral neuropathy and hepatotoxicity, are associated with isoniazid therapy, limiting its use in tuberculosis. Isoniazid is acetylated in vivo producing hydrazine and acetyl hydrazine, which are responsible for hepatotoxicity. Marked pharmacogenetic differences in acetylation have been reported among different population across the globe. This study evaluates isoniazid acetylation patterns in tuberculosis patients receiving DOT therapy under the Revised National Tuberculosis Control Program (RNTCP) in a specialized tuberculosis hospital in north India. Of 351 patients from whom samples were taken for biochemical analysis of adverse events, 36 were assessed for acetylation patterns. Blood samples were taken 1 h after administration of a 600 mg dose of isoniazid, and plasma concentrations of isoniazid were determined using a validated HPLC method. Of these 36 patients, 20 (55.56%) were slow acetylators and 16 (44.44%) were fast acetylators. Our results are consistent with those of an earlier study conducted in a different region of India. Most biochemical changes produced during long-term isoniazid therapy resolve after therapy is terminated.
Centaurea bruguierana
, of the
Asteraceae
family, has a long history of use in traditional medicines for the treatment of various ailments. However, the anticancer activity and underlying mechanisms ...have not yet been assessed. The
C. bruguierana
was extracted with methanol and fractionated into four different fractions. Different cancer cells and one non-cancerous were used to examine the cytotoxic effects of these fractions using MTT assay. The most potent fraction,
C. bruguierana
ethyl acetate fraction (CB EtOAc), was explored for its effects on cell cycle progression and apoptosis induction by Hoechst staining and annexin V-PI double staining in MCF-7 cells. The expression of apoptosis-related genes was quantified by RT-PCR. Of all fractions, CB EtOAc was found to have the strongest antiproliferative activity (IC
50
= 10 μg/mL) against MCF-7 cells. The antiproliferative activity of the CB EtOAc fraction against MCF-7 was correlated with arrested of cell cycle in the G1 phase, nuclear fragmentation, and the exposure of phosphatidylserine. The induction of apoptosis by CB EtOAc in MCF-7 cells was also associated with an increase in the Bax/Bcl-2 ratio and higher expression of caspases. Overall, our results demonstrated that CB EtOAc showed apoptosis-inducing effects, suggesting that
C. bruguierana
may be a promising source for a novel chemotherapeutic agents for the treatment of breast cancer.
Carum carvi is a well-known herb traditionally used as a spice in Asian countries. Acetaminophen is a known marketed drug mainly used as an analgesic. It has been scientifically proven that ...consumption of acetaminophen (paracetamol) is associated with liver toxicity if taken in high doses without medical supervision. The present study evaluated the in vivo antioxidant and hepatoprotective efficacy of Carum carvi against acetaminophen-induced hepatotoxicity in Wistar rats. Our results demonstrate that Carum carvi, at doses (mg/kg) of 100 (D1) and 200 (D2), showed inhibitory properties for DNA-sugar damage, lipid peroxidation, DPPH scavenging, and increased reducing potential in a concentration-dependent manner. Our results also confirm that liver toxicity associated with paracetamol, such as depletion of reduced glutathione and antioxidant enzyme levels, as well as induction of cytochrome P450, oxidative stress, apoptosis, and inflammatory cytokines, was efficiently restored by Carum carvi treatment in rats. Moreover, the expression of redox-sensitive transcription factors, namely, NF-κB and TNF-α levels, was also modulated by Carum carvi in the rats. In summary, our study confirms that Carum carvi inhibits inflammation and oxidative stress, thereby protecting liver cells from paracetamol prompted hepatotoxicity.
•Socio-economic status is very important in patient receiving DOT therapy.•Income influences disease occurrence as well as adverse events.•Occupation increases the risk of diseases and results ...increase risk of adverse events.•Low income results mal nutrition and increased risk of drug intolerance or adverse events.•DOTS is an effective treatment strategy for MTB patients.
First-line antituberculosis (anti-TB) compounds have been considered as proven components of the Directly Observed Treatment-Short course (DOTS). Drug therapy against tuberculosis has been categorized as I, II, or III following the Revised National Tuberculosis Control Program guidelines. Anti-TB are drugs are quite common and show limited adverse effects. However, first-line anti-TB compounds mediated DOTS therapy and were found with several complications. Thus, those drugs have been discontinued. Therefore, the present study was designed to find out the possible impact of socioeconomic, income, and educational status on the adverse effects of drugs and their therapeutic episodes in patients targeted with a combination of tuberculosis intervention. This study found that an increased incidence of tuberculosis was found in patients who have finished high school, contributing to a high percentage of adverse effects. Notably, adverse events were shown maximally in poor patients compared with rich- or high-income patients. On the contrary, a high prevalence of adverse events was shown to be increased in partially skilled workers compared with full-skilled workers. Consequently, adversely considerable events were implicated to be raised in patients associated with minimal socioeconomic class. Such interesting factors would help in monitoring such events in experimental patients.
PDF
