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Can a hydrogen sulfide donor protect the liver from cyclophosphamide?

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In rats, 10-day NaHS pretreatment lowered CP-driven ALT/AST spikes and suppressed TLR2/4–JNK/NF-κB inflammatory signaling linked to hepatotoxicity.

Source

TLRs-JNK/ NF-κB Pathway Underlies the Protective Effect of the Sulfide Salt Against Liver Toxicity

Abdel-Latif R, Heeba GH, Hassanin SO, et al. · Frontiers in pharmacology · 2022

doi.org/10.3389/fphar.2022.850066Read the full paper ↗55 citationscc by

What they did

They randomized rats into control, CP, NaHS+CP, and PAG+CP groups (n=6 each), gave NaHS or PAG for 10 days, then a single CP 200 mg/kg dose, and measured liver enzymes and TLR pathway markers.

What they found

CP raised ALT/AST; NaHS reduced enzymes (e.g., ALT 33.24 vs 49.57 U/L) and suppressed TLR2/4 with downstream JNK and NF-κB.

The limits

What it doesn't show

Rodent enzyme/pathway changes do not establish a clinical dosing regimen or human oncology safety for NaHS.

Key terms

NaHS
Sodium hydrosulfide, used as an H2S donor.
Cyclophosphamide (CP)
Alkylating chemotherapy that can injure the liver.
ALT/AST
Serum enzymes used as markers of hepatocellular injury.
TLR2/4
Toll-like receptors that amplify inflammatory signaling.
JNK
c-Jun N-terminal kinase stress pathway.
NF-κB
Transcription factor driving inflammatory gene programs.

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Rats per group:

Common questions

Animal design?

4 groups of 6 rats; CP ± NaHS or PAG.

CP dose?

Single 200 mg/kg i.p.

Enzyme effect of NaHS?

Lower ALT/AST vs CP alone.

Pathway finding?

TLR2/4, JNK, and NF-κB suppressed by NaHS.

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