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Study breakdown

The Peptide BPC 157 Reversed Atropine-Induced Pupil Dilation Through Nitric Oxide Pathways

evidence
The takeaway

BPC 157 counteracted atropine-induced pupil dilation in rats and guinea pigs without affecting normal pupil size, working through nitric oxide-mediated and cholinergic mechanisms.

No effect on normal pupils

BPC 157 selectively counteracted atropine-induced pupil dilation without altering normal pupil size, suggesting targeted pharmacological action rather than a blanket constricting effect

What the researchers found

BPC 157 administered locally (eye drops, 0.4 µg/eye) or systemically (intraperitoneal, 10 µg, 10 ng, or 10 pg/kg) had no effect on normal pupil size in either rats or guinea pigs. However, BPC 157 alone consistently counteracted atropine-induced mydriasis (pupil dilation) in both species and both routes of administration.

In its interactions with NO modulators, BPC 157 prolonged L-arginine-induced miosis (pupil constriction) and shortened L-NAME-induced miosis, demonstrating differential effects on the two arms of the NO system. When combined with L-NAME and/or L-arginine in atropine-dilated pupils, BPC 157 generally augmented their ability to counteract mydriasis. L-NAME and L-arginine independently produced miosis in normal pupils that was NO-specific (they attenuated each other when combined).

Why it matters

This study expands BPC 157’s known biological activities to include ocular control — a previously unexplored area. The finding that this peptide can reverse drug-induced pupil dilation through NO and cholinergic pathways suggests potential applications in ophthalmology. It also provides mechanistic insight into BPC 157’s interaction with the nitric oxide system, which is relevant to its broader proposed healing and protective properties.

How the study worked

Rats (Wistar) and guinea pigs received BPC 157, L-NAME (NOS inhibitor), L-arginine (NO precursor), and atropine either locally (eye drops) or systemically (intraperitoneal injection) alone or in various combinations. For normal pupil studies, treatments were given 3 minutes before assessment. For atropine studies, treatments were given at maximal mydriasis (30 minutes after 1% atropine drops). Multiple dose regimens of BPC 157 were tested (0.4 µg/eye locally; 10 µg, 10 ng, 10 pg/kg systemically).

What this study cannot tell us

All research is preclinical in rats and guinea pigs. Exact sample sizes per group were not specified in the abstract. The study comes from a single research group (Sikiric lab) that has published extensively on BPC 157. No human data exists for BPC 157’s ocular effects. The mechanism (NO-mediated and cholinergic) is proposed but not fully elucidated at the molecular level. Multiple comparison corrections for the many treatment combinations were not described.

How to read the evidence

This is a preclinical pharmacological study in two animal species (rats and guinea pigs) with multiple dosing regimens and routes. The use of two species and both local and systemic administration strengthens the findings. However, the research comes from a single lab group, sample sizes are not reported, and no human data exists.

When this study was published

Published in 2016, this study is part of a large body of BPC 157 research published by the Sikiric group over several decades. The findings remain relevant as interest in BPC 157 continues to grow, though human clinical data for this peptide remains limited.

The bigger picture

BPC 157 has been studied extensively by the Sikiric group for wound healing, gastrointestinal protection, and various organ-protective effects. This study adds ocular pharmacology to the peptide’s profile and, importantly, demonstrates that BPC 157’s effects operate through the nitric oxide system — one of the most fundamental signaling pathways in the body. Understanding this NO interaction may help explain BPC 157’s reported effects across multiple organ systems.

Questions still open

  • Could BPC 157 be developed as an eye drop to reverse pharmacological mydriasis after clinical eye examinations?
  • Does BPC 157’s nitric oxide modulation explain its reported healing effects in other tissues and organ systems?
  • Would these ocular effects translate to humans, and could BPC 157 have applications in conditions like pupil dysfunction or ocular inflammation?

Common questions

What is BPC 157 and why was it tested on eyes?
BPC 157 is a 15-amino-acid peptide originally derived from human gastric juice that has been studied for various protective and healing effects. This study tested it on eyes because BPC 157 is known to interact with the nitric oxide system, which plays a role in pupil control. The researchers wanted to see if BPC 157 could influence pupil responses.
Could BPC 157 be used to reverse dilated pupils after an eye exam?
In rats and guinea pigs, BPC 157 eye drops reversed atropine-induced pupil dilation. This is an interesting finding, but it’s only been tested in animals. Human clinical trials would be needed before BPC 157 could be considered for any ophthalmic use.

Read the original research

NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.

European journal of pharmacology, 771, 211-9

Citation

Kokot, Antonio; Zlatar, Mirna; Stupnisek, Mirjana; Drmic, Domagoj; Radic, Radivoje; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag. (2016). NO system dependence of atropine-induced mydriasis and L-NAME- and L-arginine-induced miosis: Reversal by the pentadecapeptide BPC 157 in rats and guinea pigs.. European journal of pharmacology, 771, 211-9. https://doi.org/10.1016/j.ejphar.2015.12.016