Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria

( Amaylia Oehadian ),( Prayudi Santoso ),( Dick Menzies ),( Rovina Ruslami ) 대한결핵 및 호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

Concise Clinical Review of Hematologic Toxicity of Linezolid in Multidrug-Resistant and Extensively Drug-Resistant Tuberculosis: Role of Mitochondria

Rovina Ruslami,Amaylia Oehadian,Prayudi Santoso,Dick Menzies 대한결핵및호흡기학회 2022 Tuberculosis and Respiratory Diseases Vol.85 No.2

Multidrug-resistant tuberculosis (MDR-TB) is caused by an organism that is resistant to both rifampicin and isoniazid. Extensively drug-resistant TB, a rare type of MDR-TB, is caused by an organism that is resistant to quinolone and one of group A TB drugs (i.e., linezolid and bedaquiline). In 2018, the World Health Organization revised the groupings of TB medicines and reclassified linezolid as a group A drug for the treatment of MDR-TB. Linezolid is a synthetic antimicrobial agent in the oxazolidinone class. Although linezolid has a good efficacy, it can cause substantial adverse events, especially hematologic toxicity. In both TB infection and linezolid mechanism of action, mitochondrial dysfunction plays an important role. In this concise review, characteristics of linezolid as an anti-TB drug are summarized, including its efficacy, pathogenesis of hematologic toxicity highlighting mitochondrial dysfunction, and the monitoring and management of hematologic toxicity.

Chemoradiation Related Acute Morbidity in Carcinoma Cervix and Correlation with Hematologic Toxicity: A South Indian Prospective Study

Kumaran, Aswathy,Guruvare, Shyamala,Sharan, Krishna,Rai, Lavanya,Hebbar, Shripad Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Purpose: To assess chemoradiation related acute morbidity in women with carcinoma cervix and to find and correlation between hematologic toxicity and organ system specific damage. Materials and Methods: A prospective study was carried out between August 2012 and July 2013 enrolling 79 women with cancer cervix receiving chemo-radiotherapy. Weekly assessment of acute morbidity was done using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4 and the toxicities were graded. Results: Anemia [77 (97.5%)], vomiting [75 (94.8%)] and diarrhea [72 (91.1%)], leukopenia [11 (13.9%)], cystitis [28 (35.4%], dermatitis [19 (24.1%)] and fatigue [29 (36.71%)] were the acute toxicities noted. The toxicities were most severe in $3^{rd}$ and $5^{th}$ week. All women could complete radiotherapy except two due to causes unrelated to radiation morbidity; seven (8.86%) had to discontinue chemotherapy due to leukopenia and intractable diarrhea. Though there was no correlation between anemia and other toxicities, it was found that all with leukopenia had diarrhea. Conclusions: Chemoradiation for cancer cervix is on the whole well tolerated. Leukopenia and severe diarrhea were the acute toxicities that compelled discontinuation of chemotherapy in two women. Though anemia had no correlation with gastrointestinal toxicity, all of those with leukopenia had diarrhea.

Protective Effects of Ginger Toward Cadmium-Induced Testes and Kidney Lipid Peroxidation and Hematological Impairment in Albino Rats

Frank C. Onwuka,Osaro Erhabor,M.U. Eteng,I.B. Umoh 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.7

This study was carried out to investigate the effect of oral dietary supplementation with ginger on cadmium-induced toxic effects on biochemical, hematological, and pathophysiological indices of albino rats. The effect of cadmium and cadmium/ginger treatment on lipid peroxidation was measured by malondialdehyde (MDA) levels in testes and kidney; serum activities of alkaline phosphatase (ALP), acid phosphatase (ACP), and prostatic acid phosphatase (PAP) enzyme were investigated alongside hematological indices. The results showed that cadmium induces a significant increase in both testicular and kidney MDA, whereas cadmium/ginger treatment produced a significant reversal of the effect of lipid peroxidation (P=.004). Cadmium treatment induced 75%, 78%, and 22% increases in activities of ACP, PAP, and ALP, respectively, whereas the cadmium/ginger-treated group reversed these values for enzyme activities (P=.001). Results of organ weight and hematological indices analysis in the cadmium-treated rats showed a decrease in organ weight and distortion of the hemopoietic features, whereas the cadmium/ginger-treated rats showed an improvement in organ weight and hematological indices (P=.04 and .001, respectively). The reversal of the toxic effects of cadmium in the cadmium/ginger-treated albino rats heralds the antioxidant potency of ginger toward cadmium toxicity-associated oxidative stress.

꿀벌 독의 독성 강도와 동물에 미치는 영향

김하영(Hayoung Kim),김희연(Hee-Yeon Kim),김혜주(Hyeju Kim),이규빈(Kyubin Lee),안민지(Minji An),정소연(Soyeon Jeong),이용호(Yong-Ho Lee) 한국동물보건학회 2023 한국동물보건학회지 Vol.2 No.4

Sting injury by bees or wasps have become frequent recently and have become a matter to prevent and consider in companion animal health care. Therefore, it is necessary to better understand the level of toxicity of Hymenoptera insect venom, and in this study, we were to investigate the toxicity of honey bee venom and its effects on animals through an acute toxicity test using mice. The mouse acute toxicity test was performed by intraperitoneally administering 0, 2.5, 5, and 7.5 mg/kg of bee venom to C57BL/6 mice. Body weight changes and blood glucose levels were measured before and after administration. During the administration, major common symptoms were observed. Lethal dose 50(LD50)values were calculated and blood samples were collected from sacrificed animals and used for hematologic examination to measure blood levels of ALB, ALT, AST, BUN, LDL, HDL, and total cholesterol. As a result of the mouse acute toxicity test, the LD50 value was found to be 4.48 mg/kg in male and 5.86 mg/kg in female C57BL/6 mice. Information on the toxicity of bee venom and hematological analysis results will provide basic data for the health care and emergency treatment of animals stung by bees.

Single-dose and 4-week repeated dose Toxicity of Aconitum Sinomontanum Nakai Pharmacopuncture: An Experimental Study

Sang Ha Woo,Jung Hee Lee,Cho-in Lee,이윤규,이현종,김재수 대한침구의학회 2021 대한침구의학회지 Vol.38 No.1

Background: This study aimed to assess the toxicity of Aconitum sinomontanum Nakai (ASN) pharmacopuncture. Methods: To investigate the toxicity of ASN pharmacopuncture, single and 4-week repeated dose toxicity experiments were conducted on BALB/c mice. In the single-dose toxicity experiment, mice were assigned 1 of 4 groups (5 males, 5 females per group). Then, 31.25, 62.5, and 125 mg/kg of ASN pharmacopuncture were administered to the mice in the experimental groups at acupoint ST36, while 0.2 mL of normal saline was administered to the control group at ST36. After a 4-week repeated dose regimen, the mice were assigned into 4 groups (5 males, 5 females per group). Then, 15.625, 31.25, and 62.5 mg/kg of ASN pharmacopuncture at ST36 were administered to the mice in the experimental groups, while 0.2 mL of normal saline was administered to the control group at ST36. Mortality, morbidity, general body and organ weight changes (after 4 weeks repeated dose), serum hematological and biochemical values, and histopathological changes in the liver and kidney were observed. Results: In both single and 4-week repeated dose toxicity experiments, no deaths or symptoms occurred in any of the groups. There were no significant differences between groups in terms of body and organ weights, serum hematological and biochemical values, and specific organ histopathological changes. Conclusion: ASN pharmacopuncture injection did not demonstrate significant toxicity in BALB/c mice compared with the control group, with a no-observed-adverse-effect level for a single dose of >125 mg/kg, and for 4 weeks repeated dose it was more than 62.5 mg/kg/day.

Clinical Correlation between Brain Natriutetic Peptide and Anthracyclin-induced Cardiac Toxicity

이호섭,손창배,신성훈,김양수 대한암학회 2008 Cancer Research and Treatment Vol.40 No.3

Purpose: Anthracycline can effectively treat hematologic malignancies, but has significant risk of cardiotoxicity. We measured the clinical correlation between brain natriuretic peptide (BNP) and anthracycline-induced cardiotoxicity. Materials and Methods: Between March 2005 and March 2007, 86 patients with acute leukemia, malignant lymphoma, or multiple myeloma receiving systemic chemotherapy with anthracycline were enrolled in the Department of Hemato-oncology, Kosin University Gospel Hospital. We investigated the relationship between BNP level and cardiotoxicity through echocardiography, electrocardiography, BNP levels, and symptoms of heart failure at each chemotherapy cycle. Results: Of the 86 participants (mean age, 48.5 years; range 20∼65 years), cardiotoxicity developed in 21 patients (24.4%), with 2 patients showing arrhythmia only, 17 patients with transient aspects of heart failure, and 2 patients with chronic heart failure. Cardiotoxicity related to serum BNP level, age, cumulative dose of anthracycline, accompanying chronic disease, and elevated level of troponin-I. Heart failure was more common if BNP levels reached 100 pg/ml at least once. Conclusions: The clinical correlation between BNP and cardiotoxicity was significant in patients with systemic anthracycline chemotherapy. A prospective clinical trial will be needed to identify the causal relationship between serum BNP level and cardiotoxicity.

Non-toxic nature of chebulinic acid on biochemical, hematological and histopathological analysis in normal Sprague Dawley rats

Aamir Khurram,Sugumar Vaisnevee,Khan Hidayat Ullah,Looi Chung Yeng,Juneja Rajesh,Waqas Muhammad,Arya Aditya 한국독성학회 2022 Toxicological Research Vol.38 No.2

Chebulinic acid (CA) is an ellagitannins isolated from the dried fruits of Terminalia chebula with diverse pharmacological activities. The present study focused on the acute toxicity of CA in normal Sprague Dawley (SD) rats. CA was administered via oral gavage to different groups in 300 and 2000 mg/kg body weight and vehicle respectively. All the animals were monitored carefully for any physiological or behavioral changes for 14 days. On day 15th animals were euthanized and blood was collected for hematological and biochemical analysis. Different tissues were collected for histopathological study using four different staining techniques (hematoxylin and eosin, Masson’s trichrome, periodic acid Schiff and picro sirius red) to observe any pathological alterations. The results highlighted no morbidity and mortality after oral ingestion of CA (300 and 2000 mg/kg). Food and water consumption, body weight, relative organ weight, hematological and biochemical parameters were normal without any gross pathological lesions in harvested tissues. The outcome of the current study supported safety of CA even at high dose. However, further detailed study is required on experimentally disease model to unfold its therapeutic potential in laboratory animals.

Reference Data of the Main Physiological Parameters in Control Sprague-Dawley Rats from Pre-clinical Toxicity Studies

Zhong-Ze Han,Hong-De Xu,Kwang-Ho Kim,Tae-Hwan Ahn,Jin-Sook Bae,Ji-Young Lee,Ki-Hyun Gil,Joo-Young Lee,Su-Jung Woo,Hyun-Jung Yoo,Hyun-Kul Lee,Kap-Ho Kim,Chan-Koo Park,Hu-Song Zhang,Si-Whan Song 한국실험동물학회 2010 Laboratory Animal Research Vol.26 No.2

The purpose of this paper is to provide reference data related to the body weight, food & water consumptions, urinalysis, hematology and serum biochemistry parameters and absolute & relative organ weights obtained from control Sprague-Dawley rats, used in the 4-week and 13-week repeated-dose toxicity studies conducted in our laboratory between 2005 and 2008. The mean, standard deviation, minimum and maximum range values for hematology and serum biochemistry parameters, data of absolute & relative organ weights, and the difference between sexes and study duration of week 4 versus 13 week are presented. The studies were conducted according to “the standards of Toxicity Study for Medicinal Products” (2005) and The KFDA Notification No. 2000-63 ‘Good Laboratory Practice (GLP)’ (2000) issued by KFDA. These data could be used as reference material of Sprague-Dawley rats by conducting the studies to evaluate the toxicological profile of pre-clinical toxicity studies.

항나요법중 DDS에 의한 용혈성 빈혈 1예

박성민,이태경,문두찬,권경술,정태안 大韓癩學會 1988 癩學 會誌 Vol.21 No.1