L-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC)

Abd-Allah, Adel R. A.; Al-Majed, Abdulhakeem A.; Al-Yahya, Abdulaziz A.; Fouda, Soliman I.; Al-Shabana, Othman A.

doi:10.1007/s00204-004-0643-3

Cited by 48 publications

(26 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This may not only enhance antitumour activity of carboplatin, but it may also increase haematological toxicity. This hypothesis is supported by the effect of L-carnitine, which protects against carboplatin-induced myelosuppression by increasing the intracellular glutathione content during treatment with carboplatin (Abd-Allah et al, 2005).…”

Section: Discussionmentioning

confidence: 86%

A phase I and pharmacokinetic study of indisulam in combination with carboplatin

et al. 2007

View full text Add to dashboard Cite

Indisulam (E7070) is an anticancer agent that is currently being evaluated in phase II clinical studies. A significant reduction in glutathione synthetase and glutathione reductase transcripts by indisulam provided a molecular basis for its combination with platinum agents. Indisulam demonstrated high anti-tumour activity in various preclinical cancer models. The objectives of this study were (1) to determine the recommended dose of indisulam in combination with carboplatin in patients with solid tumours and (2) to evaluate the pharmacokinetics of the combination. Patients with solid tumours were treated with indisulam in combination with carboplatin. Indisulam (350, 500, or 600 mg m À2 ) was given as a 1-hour intravenous infusion on day 1 and carboplatin (5 or 6 mg min ml À1 ) as an intravenous infusion over 30 min on day 2 of a three-weekly cycle. Sixteen patients received study treatment and were eligible. Thrombocytopenia was the major dose limiting toxicity followed by neutropenia. Both drugs contributed to the myelosuppressive effect of the combination. Indisulam 500 mg m À2 in combination with carboplatin 6 mg min ml À1 was identified not to cause dose limiting toxicity, but a delay of re-treatment by 1 week was required regularly to allow recovery from myelosuppression. The recommended dose and schedule for an envisaged phase II study in patients with non-small cell lung cancer is indisulam 500 mg m À2 in combination with carboplatin 6 mg min ml À1 repeated four-weekly. Patients who do not experience severe thrombocytopenia at cycle 1 will be permitted to receive an escalated dose of indisulam of 600 mg m À2 from cycle 2 onwards.

show abstract

Section: Discussionmentioning

confidence: 86%

A phase I and pharmacokinetic study of indisulam in combination with carboplatin

et al. 2007

View full text Add to dashboard Cite

show abstract

“…On the other hand, numerous in vitro experiments have demonstrated that carnitine and its derivatives acetylcarnitine (Fig. 3B) and propionylcarnitine have anti-apoptotic properties [78][79][80], most likely by preventing SM breakdown and consequent Cer synthesis; this effect seems to be specific for aSMase [reviewed in 81].…”

Section: (A) Acidic Sphingomyelinase Inhibitorsmentioning

confidence: 99%

Ceramide Involvement in Apoptosis and Apoptotic Diseases

Thevissen¹,

François²,

Winderickx³

et al. 2006

MRMC

View full text Add to dashboard Cite

Apoptosis is implicated in a number of diseases, including neurodegenerative diseases and AIDS. More and more, evidence is accumulating pointing to the critical role of ceramides in the induction of apoptosis. The present review summarizes (i) the molecular basis and regulation of the apoptotic machinery, (ii) the molecular role of ceramides in the induction or execution of apoptotic pathways, and (iii) evidence linking ceramide generation to various apoptotic diseases. Additionally, this review discusses putative therapeutic approaches inhibiting ceramide production in apoptotic diseases.

show abstract

“…However, besides this well-known effect, there is growing evidence that L-carnitine also plays a role in other physiological processes in humans and animals. Indeed, L-carnitine and some of its acyl esters act as very potent reactive oxygen species scavengers25,26 and are known to have immunomodulatory properties in mammalian as well as avian species 27. Although recent studies have attended to the role of L-carnitine in treatment of male infertility during sepsis, the exact mode of action still needs to be explored.…”

Section: Introductionmentioning

confidence: 99%

Pro‐Inflammatory and Oxidative Stress Pathways which Compromise Sperm Motility and Survival May Be Altered by L‐Carnitine

Abd-Allah

Helal

Al-Yahya

et al. 2009

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2nd group was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients.

show abstract

L-Carnitine halts apoptosis and myelosuppression induced by carboplatin in rat bone marrow cell cultures (BMC)

Cited by 48 publications

References 38 publications

A phase I and pharmacokinetic study of indisulam in combination with carboplatin

A phase I and pharmacokinetic study of indisulam in combination with carboplatin

Ceramide Involvement in Apoptosis and Apoptotic Diseases

Pro‐Inflammatory and Oxidative Stress Pathways which Compromise Sperm Motility and Survival May Be Altered by L‐Carnitine

Contact Info

Product

Resources

About